Therapeutic promise of engineered nonsense suppressor tRNAs

Overview

Joseph J. Porter, Christina S. Heil, John D. Lueck

Published Online: Feb 11 2021

DOI: 10.1002/wrna.1641

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract Nonsense mutations change an amino acid codon to a premature termination codon (PTC) generally through a single‐nucleotide substitution. The generation of a PTC results in a defective truncated protein and often in severe forms of disease. Because of the exceedingly high prevalence of nonsense‐associated diseases and a unifying mechanism, there has been a concerted effort to identify PTC therapeutics. Most clinical trials for PTC therapeutics have been conducted with small molecules that promote PTC read through and incorporation of a near‐cognate amino acid. However, there is a need for PTC suppression agents that recode PTCs with the correct amino acid while being applicable to PTC mutations in many different genomic landscapes. With these characteristics, a single therapeutic will be able to treat several disease‐causing PTCs. In this review, we will focus on the use of nonsense suppression technologies, in particular, suppressor tRNAs (sup‐tRNAs), as possible therapeutics for correcting PTCs. Sup‐tRNAs have many attractive qualities as possible therapeutic agents although there are knowledge gaps on their function in mammalian cells and technical hurdles that need to be overcome before their promise is realized. This article is categorized under: RNA Processing > tRNA Processing Translation > Translation Regulation

The applications of sup‐tRNAs and their function in translation. (a) Genetic code expansion involves the codon specific incorporation of a noncanonical amino acid (ncAA) into proteins in vivo. This is accomplished by introducing an orthogonal aminoacyl‐tRNA synthetase (o‐aaRS) specific for both the ncAA and its cognate orthogonal tRNA (o‐tRNA). This newly introduced pair is “orthogonal” as it does not cross‐react with any of the endogenous tRNAs or aaRSs. For genetic code expansion, the o‐tRNA most often is engineered as an amber sup‐tRNA to ensure site‐specific ncAA incorporation. In contrast, ACE‐tRNAs for therapeutic suppression of PTCs are designed to cross‐react with endogenous aaRSs while altering the anticodon to suppress a nonsense codon. (b) Genetic code expansion enables site‐specific incorporation of an ncAA by employing an o‐aaRS/amber nonsense suppressor o‐tRNA pair to suppress an amber stop codon in the mRNA of a gene of interest using cellular translation. (c) Premature termination codons (PTCs) arise from single nucleotide mutations that convert a canonical triplet nucleotide codon into a stop codon. The generation of a PTC in an mRNA causes the translating ribosome to stop, resulting in the release of a truncated protein and mRNA degradation by nonsense‐mediated decay (NMD). (d) in a manner analogous to genetic code expansion, sup‐tRNAs are charged by an endogenous aaRS leading to PTC suppression on the ribosome, seamless rescue of full‐length protein expression, and stabilization of mRNA by inhibiting NMD

[ Normal View | Magnified View ]

Pros and cons of sup‐tRNA delivery options. For specific elements necessary for sup‐tRNA expression from DNA or virus see Figure 2(a) or Lueck et al. (2019)

[ Normal View | Magnified View ]

Diagram of structural and functional elements of a mammalian tRNA gene, processes involved with mammalian tRNA biogenesis, and tRNA function in translation. (a) Diagram of a typical tRNA gene containing an upstream control element containing a TATA‐box, transcription start site (TSS), 5′‐leader sequence, tRNA sequence containing internal A‐ and B‐box promoter elements, the location of the anticodon, intron, and variable loop, 3′‐trailer, and poly‐thymidine transcriptional terminator (p[T]). (b) Mammalian tRNAs are synthesized as a primary RNA transcript containing 5′‐leaders removed by RNase P, introns spliced out by the SEN complex, and 3′‐trailer removed by RNase Z or other exonucleases. The RNA chaperone La protein binds the poly‐uridine tracts at the 3′ ends of the primary transcript to stabilize the transcript and direct processing. The 3′‐terminal CCA trinucleotide common to all tRNAs is ligated to the pre‐tRNA during processing. Throughout the tRNA maturation process, 10–15 nucleotides are chemically modified by specific modification enzymes. (c) Following processing, tRNAs are aminoacylated by their cognate aminoacyl‐tRNA synthetase (aaRS), transported to the ribosome by EF1a, and finally participate in translation on the ribosome

[ Normal View | Magnified View ]

References

Adachi,, M., & Cavalcanti,, A. R. (2009). Tandem stop codons in ciliates that reassign stop codons. Journal of Molecular Evolution, 68(4), 424–431. https://doi.org/10.1007/s00239-009-9220-y
Amrani,, N., Ganesan,, R., Kervestin,, S., Mangus,, D. A., Ghosh,, S., & Jacobson,, A. (2004). A faux 3`‐UTR promotes aberrant termination and triggers nonsense‐mediated mRNA decay. Nature, 432(7013), 112–118. https://doi.org/10.1038/nature03060
Anderson,, J. C., Wu,, N., Santoro,, S. W., Lakshman,, V., King,, D. S., & Schultz,, P. G. (2004). An expanded genetic code with a functional quadruplet codon. Proceedings of the National Academy of Sciences of the United States of America, 101(20), 7566–7571. https://doi.org/10.1073/pnas.0401517101
Anderson,, W. F., Gorini,, L., & Breckenridge,, L. (1965). Role of ribosomes in streptomycin‐activated suppression. Proceedings of the National Academy of Sciences of the United States of America, 54(4), 1076–1083. https://doi.org/10.1073/pnas.54.4.1076
Ashton,, L. J., Brooks,, D. A., McCourt,, P. A., Muller,, V. J., Clements,, P. R., & Hopwood,, J. J. (1992). Immunoquantification and enzyme kinetics of alpha‐L‐iduronidase in cultured fibroblasts from normal controls and mucopolysaccharidosis type I patients. American Journal of Human Genetics, 50(4), 787–794.
Atanasova,, V. S., Jiang,, Q., Prisco,, M., Gruber,, C., Pinon Hofbauer,, J., Chen,, M., Has,, C., Bruckner‐Tuderman,, L., McGrath,, J. A., Uitto,, J., & South,, A. P. (2017). Amlexanox enhances premature termination codon read‐through in COL7A1 and expression of full length type VII collagen: Potential therapy for recessive dystrophic Epidermolysis Bullosa. The Journal of Investigative Dermatology, 137(9), 1842–1849. https://doi.org/10.1016/j.jid.2017.05.011
Barton‐Davis,, E. R., Cordier,, L., Shoturma,, D. I., Leland,, S. E., & Sweeney,, H. L. (1999). Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. The Journal of Clinical Investigation, 104(4), 375–381. https://doi.org/10.1172/JCI7866
Bazzani,, R. P., Pringle,, I. A., Connolly,, M. M., Davies,, L. A., Sumner‐Jones,, S. G., Schleef,, M., Hyde,, S. C., & Gill,, D. R. (2016). Transgene sequences free of CG dinucleotides lead to high level, long‐term expression in the lung independent of plasmid backbone design. Biomaterials, 93, 20–26. https://doi.org/10.1016/j.biomaterials.2016.03.029
Bedwell,, D. M., Kaenjak,, A., Benos,, D. J., Bebok,, Z., Bubien,, J. K., Hong,, J., Tousson,, A., Clancy,, J. P., & Sorscher,, E. J. (1997). Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nature Medicine, 3(11), 1280–1284. https://doi.org/10.1038/nm1197-1280
Beier,, H., & Grimm,, M. (2001). Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Research, 29(23), 4767–4782. https://doi.org/10.1093/nar/29.23.4767
Bellais,, S., Le Goff,, C., Dagoneau,, N., Munnich,, A., & Cormier‐Daire,, V. (2010). In vitro readthrough of termination codons by gentamycin in the Stuve‐Wiedemann syndrome. European Journal of Human Genetics, 18(1), 130–132. https://doi.org/10.1038/ejhg.2009.122
Bianco,, A., Townsley,, F. M., Greiss,, S., Lang,, K., & Chin,, J. W. (2012). Expanding the genetic code of Drosophila melanogaster. Nature Chemical Biology, 8(9), 748–750. https://doi.org/10.1038/nchembio.1043
Bienz,, M., Kubli,, E., Kohli,, J., de Henau,, S., & Grosjean,, H. (1980). Nonsense suppression in eukaryotes: The use of the Xenopus oocyte as an in vivo assay system. Nucleic Acids Research, 8(22), 5169–5178. https://doi.org/10.1093/nar/8.22.5169
Bonetti,, B., Fu,, L., Moon,, J., & Bedwell,, D. M. (1995). The efficiency of translation termination is determined by a synergistic interplay between upstream and downstream sequences in Saccharomyces cerevisiae. Journal of Molecular Biology, 251(3), 334–345. https://doi.org/10.1006/jmbi.1995.0438
Bordeira‐Carrico,, R., Ferreira,, D., Mateus,, D. D., Pinheiro,, H., Pego,, A. P., Santos,, M. A., & Oliveira,, C. (2014). Rescue of wild‐type E‐cadherin expression from nonsense‐mutated cancer cells by a suppressor‐tRNA. European Journal of Human Genetics, 22(9), 1085–1092. https://doi.org/10.1038/ejhg.2013.292
Brantly,, M. L., Chulay,, J. D., Wang,, L., Mueller,, C., Humphries,, M., Spencer,, L. T., Rouhani,, F., Conlon,, T. J., Calcedo,, R., Betts,, M. R., Spencer,, C., Byrne,, B. J., Wilson,, J. M., & Flotte,, T. R. (2009). Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1‐AAT gene therapy. Proceedings of the National Academy of Sciences of the United States of America, 106(38), 16363–16368. https://doi.org/10.1073/pnas.0904514106
Brenner,, S., Barnett,, L., Katz,, E. R., & Crick,, F. H. (1967). UGA: A third nonsense triplet in the genetic code. Nature, 213(5075), 449–450. https://doi.org/10.1038/213449a0
Brenner,, S., Stretton,, A. O., & Kaplan,, S. (1965). Genetic code: The ‘nonsense’ triplets for chain termination and their suppression. Nature, 206(988), 994–998. https://doi.org/10.1038/206994a0
Brown,, W., & Deiters,, A. (2019). Light‐activation of Cre recombinase in zebrafish embryos through genetic code expansion. Methods in Enzymology, 624, 265–281. https://doi.org/10.1016/bs.mie.2019.04.004
Bulfield,, G., Siller,, W. G., Wight,, P. A., & Moore,, K. J. (1984). X chromosome‐linked muscular dystrophy (mdx) in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 81(4), 1189–1192. https://doi.org/10.1073/pnas.81.4.1189
Bunge,, S., Clements,, P. R., Byers,, S., Kleijer,, W. J., Brooks,, D. A., & Hopwood,, J. J. (1998). Genotype‐phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochimica et Biophysica Acta, 1407(3), 249–256. https://doi.org/10.1016/s0925-4439(98)00046-5
Buvoli,, M., Buvoli,, A., & Leinwand,, L. A. (2000). Suppression of nonsense mutations in cell culture and mice by multimerized suppressor tRNA genes. Molecular and Cellular Biology, 20(9), 3116–3124. https://doi.org/10.1128/mcb.20.9.3116-3124.2000
Capecchi,, M. R., & Gussin,, G. N. (1965). Suppression in vitro: Identification of a serine‐sRNA as a "nonsense" suppressor. Science, 149(3682), 417–422. https://doi.org/10.1126/science.149.3682.417
Capecchi,, M. R., Haar,, R. A., Capecchi,, N. E., & Sveda,, M. M. (1977). The isolation of a suppressible nonsense mutant in mammalian cells. Cell, 12(2), 371–381. https://doi.org/10.1016/0092-8674(77)90113-1
Capecchi,, M. R., Hughes,, S. H., & Wahl,, G. M. (1975). Yeast super‐suppressors are altered tRNAs capable of translating a nonsense codon in vitro. Cell, 6(3), 269–277. https://doi.org/10.1016/0092-8674(75)90178-6
Cassan,, M., & Rousset,, J. P. (2001). UAG readthrough in mammalian cells: Effect of upstream and downstream stop codon contexts reveal different signals. BMC Molecular Biology, 2, 3. https://doi.org/10.1186/1471-2199-2-3
Celik,, A., Kervestin,, S., & Jacobson,, A. (2015). NMD: At the crossroads between translation termination and ribosome recycling. Biochimie, 114, 2–9. https://doi.org/10.1016/j.biochi.2014.10.027
Chamberlain,, J. S. (1997). Dystrophin levels required for genetic correction of Duchenne muscular dystrophy. Basic and Applied Myology, 7, 251–255.
Chang,, J. C., & Kan,, Y. W. (1979). Beta 0 thalassemia, a nonsense mutation in man. Proceedings of the National Academy of Sciences of the United States of America, 76(6), 2886–2889. https://doi.org/10.1073/pnas.76.6.2886
Chatterjee,, A., Xiao,, H., Bollong,, M., Ai,, H. W., & Schultz,, P. G. (2013). Efficient viral delivery system for unnatural amino acid mutagenesis in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America, 110(29), 11803–11808. https://doi.org/10.1073/pnas.1309584110
Chatterjee,, K., Majumder,, S., Wan,, Y., Shah,, V., Wu,, J., Huang,, H. Y., & Hopper,, A. K. (2017). Sharing the load: Mex67‐Mtr2 cofunctions with Los1 in primary tRNA nuclear export. Genes %26 Development, 31(21), 2186–2198. https://doi.org/10.1101/gad.305904.117
Chatterjee,, K., Nostramo,, R. T., Wan,, Y., & Hopper,, A. K. (2018). tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location. Biochimica et Biophysica Acta, Gene Regulatory Mechanisms, 1861(4), 373–386. https://doi.org/10.1016/j.bbagrm.2017.11.007
Chemla,, Y., Ozer,, E., Algov,, I., & Alfonta,, L. (2018). Context effects of genetic code expansion by stop codon suppression. Current Opinion in Chemical Biology, 46, 146–155. https://doi.org/10.1016/j.cbpa.2018.07.012
Chen,, Y., Ma,, J., Lu,, W., Tian,, M., Thauvin,, M., Yuan,, C., Volovitch,, M., Wang,, Q., Holst,, J., Liu,, M., Vriz,, S., Ye,, S., Wang,, L., & Li,, D. (2017). Heritable expansion of the genetic code in mouse and zebrafish. Cell Research, 27(2), 294–297. https://doi.org/10.1038/cr.2016.145
Chen,, Z., Ulmasov,, B., & Folk,, W. R. (1998). Nonsense and missense translational suppression in plant cells mediated by tRNA(Lys). Plant Molecular Biology, 36(1), 163–170. https://doi.org/10.1023/a:1005996125011
Chittum,, H. S., Lane,, W. S., Carlson,, B. A., Roller,, P. P., Lung,, F. D., Lee,, B. J., & Hatfield,, D. L. (1998). Rabbit beta‐globin is extended beyond its UGA stop codon by multiple suppressions and translational reading gaps. Biochemistry, 37(31), 10866–10870. https://doi.org/10.1021/bi981042r
Cideciyan,, A. V. (2010). Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Progress in Retinal and Eye Research, 29(5), 398–427. https://doi.org/10.1016/j.preteyeres.2010.04.002
Copela,, L. A., Fernandez,, C. F., Sherrer,, R. L., & Wolin,, S. L. (2008). Competition between the Rex1 exonuclease and the La protein affects both Trf4p‐mediated RNA quality control and pre‐tRNA maturation. RNA, 14(6), 1214–1227. https://doi.org/10.1261/rna.1050408
Cosson,, B., Couturier,, A., Chabelskaya,, S., Kiktev,, D., Inge‐Vechtomov,, S., Philippe,, M., & Zhouravleva,, G. (2002). Poly(a)‐binding protein acts in translation termination via eukaryotic release factor 3 interaction and does not influence [PSI(+)] propagation. Molecular and Cellular Biology, 22(10), 3301–3315. https://doi.org/10.1128/mcb.22.10.3301-3315.2002
Crawford,, D., Alroy,, I., Sharpe,, N., Goddeeris,, M., & Williams,, G. (2020). ELX‐02 generates protein via premature stop codon read‐through without inducing native stop codon read‐through proteins. The Journal of Pharmacology and Experimental Therapeutics, 374, 264–272. https://doi.org/10.1124/jpet.120.265595
Cremer,, K. J., Bodemer,, M., Summers,, W. P., Summers,, W. C., & Gesteland,, R. F. (1979). In vitro suppression of UAG and UGA mutants in the thymidine kinase gene of herpes simplex virus. Proceedings of the National Academy of Sciences of the United States of America, 76(1), 430–434. https://doi.org/10.1073/pnas.76.1.430
Cropp,, T. A., & Schultz,, P. G. (2004). An expanding genetic code. Trends in Genetics, 20(12), 625–630. https://doi.org/10.1016/j.tig.2004.09.013
Dabrowski,, M., Bukowy‐Bieryllo,, Z., & Zietkiewicz,, E. (2015). Translational readthrough potential of natural termination codons in eucaryotes—The impact of RNA sequence. RNA Biology, 12(9), 950–958. https://doi.org/10.1080/15476286.2015.1068497
Dabrowski,, M., Bukowy‐Bieryllo,, Z., & Zietkiewicz,, E. (2018). Advances in therapeutic use of a drug‐stimulated translational readthrough of premature termination codons. Molecular Medicine, 24(1), 25. https://doi.org/10.1186/s10020-018-0024-7
Dalpke,, A., & Helm,, M. (2012). RNA mediated toll‐like receptor stimulation in health and disease. RNA Biology, 9(6), 828–842. https://doi.org/10.4161/rna.20206
Davies,, J., Gilbert,, W., & Gorini,, L. (1964). Streptomycin, suppression, and the code. Proceedings of the National Academy of Sciences of the United States of America, 51(5), 883–890. https://doi.org/10.1073/pnas.51.5.883
Dean,, D. A. (2003). Electroporation of the vasculature and the lung. DNA and Cell Biology, 22(12), 797–806. https://doi.org/10.1089/104454903322625000
Dean,, D. A. (2005). Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals. American Journal of Physiology. Cell Physiology, 289(2), C233–C245. https://doi.org/10.1152/ajpcell.00613.2004
Dever,, T. E., & Green,, R. (2012). The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harbor Perspectives in Biology, 4(7), a013706. https://doi.org/10.1101/cshperspect.a013706
Dieci,, G., Fiorino,, G., Castelnuovo,, M., Teichmann,, M., & Pagano,, A. (2007). The expanding RNA polymerase III transcriptome. Trends in Genetics, 23(12), 614–622. https://doi.org/10.1016/j.tig.2007.09.001
Dittmar,, K. A., Goodenbour,, J. M., & Pan,, T. (2006). Tissue‐specific differences in human transfer RNA expression. PLoS Genetics, 2(12), e221. https://doi.org/10.1371/journal.pgen.0020221
Dumas,, A., Lercher,, L., Spicer,, C. D., & Davis,, B. G. (2015). Designing logical codon reassignment—Expanding the chemistry in biology. Chemical Science, 6(1), 50–69. https://doi.org/10.1039/c4sc01534g
Durand,, S., Cougot,, N., Mahuteau‐Betzer,, F., Nguyen,, C. H., Grierson,, D. S., Bertrand,, E., Tazi,, J., & Lejeune,, F. (2007). Inhibition of nonsense‐mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P‐bodies. The Journal of Cell Biology, 178(7), 1145–1160. https://doi.org/10.1083/jcb.200611086
Edwards,, H., & Schimmel,, P. (1990). A bacterial amber suppressor in Saccharomyces cerevisiae is selectively recognized by a bacterial aminoacyl‐tRNA synthetase. Molecular and Cellular Biology, 10(4), 1633–1641. https://doi.org/10.1128/mcb.10.4.1633
Ellefson,, J. W., Meyer,, A. J., Hughes,, R. A., Cannon,, J. R., Brodbelt,, J. S., & Ellington,, A. D. (2014). Directed evolution of genetic parts and circuits by compartmentalized partnered replication. Nature Biotechnology, 32(1), 97–101. https://doi.org/10.1038/nbt.2714
Elliott,, T. S., Bianco,, A., & Chin,, J. W. (2014). Genetic code expansion and bioorthogonal labelling enables cell specific proteomics in an animal. Current Opinion in Chemical Biology, 21, 154–160. https://doi.org/10.1016/j.cbpa.2014.07.001
Elsasser,, S. J., Ernst,, R. J., Walker,, O. S., & Chin,, J. W. (2016). Genetic code expansion in stable cell lines enables encoded chromatin modification. Nature Methods, 13(2), 158–164. https://doi.org/10.1038/nmeth.3701
Engelhardt,, D. L., Webster,, R. E., Wilhelm,, R. C., & Zinder,, N. (1965). In vitro studies on the mechanism of suppression of a nonsense mutation. Proceedings of the National Academy of Sciences of the United States of America, 54(6), 1791–1797. https://doi.org/10.1073/pnas.54.6.1791
Epstein,, R. H., Bolle,, A., & Steinberg,, C. M. (2012). Amber mutants of bacteriophage T4D: Their isolation and genetic characterization. Genetics, 190(3), 833–840. https://doi.org/10.1534/genetics.112.138438
Ernst,, R. J., Krogager,, T. P., Maywood,, E. S., Zanchi,, R., Beranek,, V., Elliott,, T. S., Barry,, N. P., Hastings,, M. H., & Chin,, J. W. (2016). Genetic code expansion in the mouse brain. Nature Chemical Biology, 12(10), 776–778. https://doi.org/10.1038/nchembio.2160
Fang,, K. Y., Lieblich,, S. A., & Tirrell,, D. A. (2018). Incorporation of non‐canonical amino acids into proteins by global reassignment of sense codons. Methods in Molecular Biology, 1798, 173–186. https://doi.org/10.1007/978-1-4939-7893-9_13
Fang,, Y., Bateman,, J. F., Mercer,, J. F., & Lamande,, S. R. (2013). Nonsense‐mediated mRNA decay of collagen ‐emerging complexity in RNA surveillance mechanisms. Journal of Cell Science, 126(Pt 12), 2551–2560.doi:https://doi.org/10.1242/jcs.120220
Fan‐Minogue,, H., & Bedwell,, D. M. (2008). Eukaryotic ribosomal RNA determinants of aminoglycoside resistance and their role in translational fidelity. RNA, 14(1), 148–157. https://doi.org/10.1261/rna.805208
Feldman,, A. W., Dien,, V. T., Karadeema,, R. J., Fischer,, E. C., You,, Y., Anderson,, B. A., Krishnamurthy,, R., Chen,, J. S., Li,, L., & Romesberg,, F. E. (2019). Optimization of replication, transcription, and translation in a semi‐synthetic organism. Journal of the American Chemical Society, 141(27), 10644–10653. https://doi.org/10.1021/jacs.9b02075
Fernandez,, I. S., Ng,, C. L., Kelley,, A. C., Wu,, G., Yu,, Y. T., & Ramakrishnan,, V. (2013). Unusual base pairing during the decoding of a stop codon by the ribosome. Nature, 500(7460), 107–110. https://doi.org/10.1038/nature12302
Floquet,, C., Hatin,, I., Rousset,, J. P., & Bidou,, L. (2012). Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin. PLoS Genetics, 8(3), e1002608. https://doi.org/10.1371/journal.pgen.1002608
Francois,, B., Russell,, R. J., Murray,, J. B., Aboul‐ela,, F., Masquida,, B., Vicens,, Q., & Westhof,, E. (2005). Crystal structures of complexes between aminoglycosides and decoding a site oligonucleotides: Role of the number of rings and positive charges in the specific binding leading to miscoding. Nucleic Acids Research, 33(17), 5677–5690. https://doi.org/10.1093/nar/gki862
Freund,, I., Eigenbrod,, T., Helm,, M., & Dalpke,, A. H. (2019). RNA modifications modulate activation of innate toll‐like receptors. Genes (Basel), 10(2), 1–18. https://doi.org/10.3390/genes10020092
Frischmeyer‐Guerrerio,, P. A., Montgomery,, R. A., Warren,, D. S., Cooke,, S. K., Lutz,, J., Sonnenday,, C. J., Guerrerio,, A. L., & Dietz,, H. C. (2011). Perturbation of thymocyte development in nonsense‐mediated decay (NMD)‐deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 108(26), 10638–10643. https://doi.org/10.1073/pnas.1019352108
Furter,, R. (1998). Expansion of the genetic code: Site‐directed p‐fluoro‐phenylalanine incorporation in Escherichia coli. Protein Science, 7(2), 419–426. https://doi.org/10.1002/pro.5560070223
Gautier,, A., Nguyen,, D. P., Lusic,, H., An,, W., Deiters,, A., & Chin,, J. W. (2010). Genetically encoded photocontrol of protein localization in mammalian cells. Journal of the American Chemical Society, 132(12), 4086–4088. https://doi.org/10.1021/ja910688s
Gesteland,, R. F., Wills,, N., Lewis,, J. B., & Grodzicker,, T. (1977). Identification of amber and ochre mutants of the human virus Ad2+ND1. Proceedings of the National Academy of Sciences of the United States of America, 74(10), 4567–4571. https://doi.org/10.1073/pnas.74.10.4567
Gill,, D. R., Smyth,, S. E., Goddard,, C. A., Pringle,, I. A., Higgins,, C. F., Colledge,, W. H., & Hyde,, S. C. (2001). Increased persistence of lung gene expression using plasmids containing the ubiquitin C or elongation factor 1alpha promoter. Gene Therapy, 8(20), 1539–1546. https://doi.org/10.1038/sj.gt.3301561
Giuliodori,, S., Percudani,, R., Braglia,, P., Ferrari,, R., Guffanti,, E., Ottonello,, S., & Dieci,, G. (2003). A composite upstream sequence motif potentiates tRNA gene transcription in yeast. Journal of Molecular Biology, 333(1), 1–20. https://doi.org/10.1016/j.jmb.2003.08.016
Gonzalez‐Hilarion,, S., Beghyn,, T., Jia,, J., Debreuck,, N., Berte,, G., Mamchaoui,, K., Mouly,, V., Gruenert,, D. C., & Lejeune,, F. (2012). Rescue of nonsense mutations by amlexanox in human cells. Orphanet Journal of Rare Diseases, 7, 58. https://doi.org/10.1186/1750-1172-7-58
Goodman,, H. M., Abelson,, J., Landy,, A., Brenner,, S., & Smith,, J. D. (1968). Amber suppression: A nucleotide change in the anticodon of a tyrosine transfer RNA. Nature, 217(5133), 1019–1024. https://doi.org/10.1038/2171019a0
Gorini,, L., & Kataja,, E. (1964). Phenotypic repair by streptomycin of defective genotypes in E. coli. Proceedings of the National Academy of Sciences of the United States of America, 51(3), 487–493. https://doi.org/10.1073/pnas.51.3.487
Goswami,, R., Subramanian,, G., Silayeva,, L., Newkirk,, I., Doctor,, D., Chawla,, K., Chattopadhyay,, S., Chandra,, D., Chilukuri,, N., & Betapudi,, V. (2019). Gene therapy leaves a vicious cycle. Frontiers in Oncology, 9, 297. https://doi.org/10.3389/fonc.2019.00297
Gotham,, V. J., Hobbs,, M. C., Burgin,, R., Turton,, D., Smythe,, C., & Coldham,, I. (2016). Synthesis and activity of a novel inhibitor of nonsense‐mediated mRNA decay. Organic %26 Biomolecular Chemistry, 14(5), 1559–1563. https://doi.org/10.1039/c5ob02482j
Greiss,, S., & Chin,, J. W. (2011). Expanding the genetic code of an animal. Journal of the American Chemical Society, 133(36), 14196–14199. https://doi.org/10.1021/ja2054034
Gromadski,, K. B., Schümmer,, T., Strømgaard,, A., Knudsen,, C. R., Kinzy,, T. G., & Rodnina,, M. V. (2007). Kinetics of the interactions between yeast elongation factors 1A and 1Balpha, guanine nucleotides, and aminoacyl‐tRNA. The Journal of Biological Chemistry, 282(49), 35629–35637. https://doi.org/10.1074/jbc.M707245200
Guo,, J., Melancon,, C. E., 3rd, Lee,, H. S., Groff,, D., & Schultz,, P. G. (2009). Evolution of amber suppressor tRNAs for efficient bacterial production of proteins containing nonnatural amino acids. Angewandte Chemie International Edition, 48(48), 9148–9151. https://doi.org/10.1002/anie.200904035
Hadd,, A., & Perona,, J. J. (2014). Recoding aminoacyl‐tRNA synthetases for synthetic biology by rational protein‐RNA engineering. ACS Chemical Biology, 9(12), 2761–2766. https://doi.org/10.1021/cb5006596
Hancock,, S. M., Uprety,, R., Deiters,, A., & Chin,, J. W. (2010). Expanding the genetic code of yeast for incorporation of diverse unnatural amino acids via a pyrrolysyl‐tRNA synthetase/tRNA pair. Journal of the American Chemical Society, 132(42), 14819–14824. https://doi.org/10.1021/ja104609m
Hatfield,, D., Thorgeirsson,, S. S., Copeland,, T. D., Oroszlan,, S., & Bustin,, M. (1988). Immunopurification of the suppressor tRNA dependent rabbit beta‐globin readthrough protein. Biochemistry, 27(4), 1179–1183. https://doi.org/10.1021/bi00404a017
Hauswirth,, W. W., Aleman,, T. S., Kaushal,, S., Cideciyan,, A. V., Schwartz,, S. B., Wang,, L., Conlon,, T. J., Boye,, S. L., Flotte,, T. R., Byrne,, B. J., & Jacobson,, S. G. (2008). Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno‐associated virus gene vector: Short‐term results of a phase I trial. Human Gene Therapy, 19(10), 979–990. https://doi.org/10.1089/hum.2008.107
Hellen,, C. U. T. (2018). Translation termination and ribosome recycling in eukaryotes. Cold Spring Harbor Perspectives in Biology, 10(10), 1–18. https://doi.org/10.1101/cshperspect.a032656
Herweijer,, H., & Wolff,, J. A. (2003). Progress and prospects: Naked DNA gene transfer and therapy. Gene Therapy, 10(6), 453–458. https://doi.org/10.1038/sj.gt.3301983
Hetz,, C. (2012). The unfolded protein response: Controlling cell fate decisions under ER stress and beyond. Nature Reviews. Molecular Cell Biology, 13(2), 89–102. https://doi.org/10.1038/nrm3270
Hino,, N., Okazaki,, Y., Kobayashi,, T., Hayashi,, A., Sakamoto,, K., & Yokoyama,, S. (2005). Protein photo‐cross‐linking in mammalian cells by site‐specific incorporation of a photoreactive amino acid. Nature Methods, 2(3), 201–206. https://doi.org/10.1038/nmeth739
Hirata,, A. (2019). Recent insights into the structure, function, and evolution of the RNA‐splicing endonucleases. Frontiers in Genetics, 10, 103. https://doi.org/10.3389/fgene.2019.00103
Hobbie,, S. N., Akshay,, S., Kalapala,, S. K., Bruell,, C. M., Shcherbakov,, D., & Bottger,, E. C. (2008). Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity. Proceedings of the National Academy of Sciences of the United States of America, 105(52), 20888–20893. https://doi.org/10.1073/pnas.0811258106
Hopper,, A. K., & Huang,, H. Y. (2015). Quality control pathways for nucleus‐encoded eukaryotic tRNA biosynthesis and subcellular trafficking. Molecular and Cellular Biology, 35(12), 2052–2058. https://doi.org/10.1128/MCB.00131-15
Hopper,, A. K., Pai,, D. A., & Engelke,, D. R. (2010). Cellular dynamics of tRNAs and their genes. FEBS Letters, 584(2), 310–317. https://doi.org/10.1016/j.febslet.2009.11.053
Hopper,, A. K., & Phizicky,, E. M. (2003). tRNA transfers to the limelight. Genes %26 Development, 17(2), 162–180. https://doi.org/10.1101/gad.1049103
Hornstein,, B. D., Roman,, D., Arévalo‐Soliz,, L. M., Engevik,, M. A., & Zechiedrich,, L. (2016). Effects of circular DNA length on transfection efficiency by electroporation into HeLa cells. PLoS One, 11(12), e0167537. https://doi.org/10.1371/journal.pone.0167537
Howard,, M., Frizzell,, R. A., & Bedwell,, D. M. (1996). Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nature Medicine, 2(4), 467–469. https://doi.org/10.1038/nm0496-467
Huang,, L., Aghajan,, M., Quesenberry,, T., Low,, A., Murray,, S. F., Monia,, B. P., & Guo,, S. (2019). Targeting translation termination machinery with antisense oligonucleotides for diseases caused by nonsense mutations. Nucleic Acid Therapeutics, 29(4), 175–186. https://doi.org/10.1089/nat.2019.0779
Huang,, L., & Wilkinson,, M. F. (2012). Regulation of nonsense‐mediated mRNA decay. WIREs RNA, 3(6), 807–828. https://doi.org/10.1002/wrna.1137
Hudziak,, R. M., Laski,, F. A., RajBhandary,, U. L., Sharp,, P. A., & Capecchi,, M. R. (1982). Establishment of mammalian cell lines containing multiple nonsense mutations and functional suppressor tRNA genes. Cell, 31(1), 137–146. https://doi.org/10.1016/0092-8674(82)90413-5
Hughes,, R. A., & Ellington,, A. D. (2010). Rational design of an orthogonal tryptophanyl nonsense suppressor tRNA. Nucleic Acids Research, 38(19), 6813–6830. https://doi.org/10.1093/nar/gkq521
Hwang,, J., & Maquat,, L. E. (2011). Nonsense‐mediated mRNA decay (NMD) in animal embryogenesis: To die or not to die, that is the question. Current Opinion in Genetics %26 Development, 21(4), 422–430. https://doi.org/10.1016/j.gde.2011.03.008
Ibba,, M., & Soll,, D. (2000). Aminoacyl‐tRNA synthesis. Annual Review of Biochemistry, 69, 617–650. https://doi.org/10.1146/annurev.biochem.69.1.617
Infield,, D. T., Lueck,, J. D., Galpin,, J. D., Galles,, G. D., & Ahern,, C. A. (2018). Orthogonality of Pyrrolysine tRNA in the Xenopus oocyte. Scientific Reports, 8(1), 5166. https://doi.org/10.1038/s41598-018-23201-z
Ivanov,, A., Mikhailova,, T., Eliseev,, B., Yeramala,, L., Sokolova,, E., Susorov,, D., Shuvalov,, A., Schaffitzel,, C., & Alkalaeva,, E. (2016). PABP enhances release factor recruitment and stop codon recognition during translation termination. Nucleic Acids Research, 44(16), 7766–7776. https://doi.org/10.1093/nar/gkw635
Ivanov,, P. V., Gehring,, N. H., Kunz,, J. B., Hentze,, M. W., & Kulozik,, A. E. (2008). Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. The EMBO Journal, 27(5), 736–747. https://doi.org/10.1038/emboj.2008.17
Jackson,, R. J., Hellen,, C. U., & Pestova,, T. V. (2012). Termination and post‐termination events in eukaryotic translation. Advances in Protein Chemistry and Structural Biology, 86, 45–93. https://doi.org/10.1016/b978-0-12-386497-0.00002-5
Johnson,, D. B., Xu,, J., Shen,, Z., Takimoto,, J. K., Schultz,, M. D., Schmitz,, R. J., Xiang,, Z., Ecker,, J. R., Briggs,, S. P., & Wang,, L. (2011). RF1 knockout allows ribosomal incorporation of unnatural amino acids at multiple sites. Nature Chemical Biology, 7(11), 779–786. https://doi.org/10.1038/nchembio.657
Kadaba,, S., Krueger,, A., Trice,, T., Krecic,, A. M., Hinnebusch,, A. G., & Anderson,, J. (2004). Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes %26 Development, 18(11), 1227–1240. https://doi.org/10.1101/gad.1183804
Kang,, J. Y., Kawaguchi,, D., Coin,, I., Xiang,, Z., O`Leary,, D. D., Slesinger,, P. A., & Wang,, L. (2013). In vivo expression of a light‐activatable potassium channel using unnatural amino acids. Neuron, 80(2), 358–370. https://doi.org/10.1016/j.neuron.2013.08.016
Karijolich,, J., & Yu,, Y. T. (2011). Converting nonsense codons into sense codons by targeted pseudouridylation. Nature, 474(7351), 395–398. https://doi.org/10.1038/nature10165
Karijolich,, J., & Yu,, Y. T. (2014). Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (review). International Journal of Molecular Medicine, 34(2), 355–362. https://doi.org/10.3892/ijmm.2014.1809
Keeling,, K. M., & Bedwell,, D. M. (2011). Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases. WIREs RNA, 2(6), 837–852. https://doi.org/10.1002/wrna.95
Keeling,, K. M., Wang,, D., Dai,, Y., Murugesan,, S., Chenna,, B., Clark,, J., Belakhov,, V., Kandasamy,, J., Velu,, S. E., Baasov,, T., & Bedwell,, D. M. (2013). Attenuation of nonsense‐mediated mRNA decay enhances in vivo nonsense suppression. PLoS One, 8(4), e60478. https://doi.org/10.1371/journal.pone.0060478
Keeling,, K. M., Xue,, X., Gunn,, G., & Bedwell,, D. M. (2014). Therapeutics based on stop codon readthrough. Annual Review of Genomics and Human Genetics, 15, 371–394. https://doi.org/10.1146/annurev-genom-091212-153527
Kerem,, E. (2004). Pharmacologic therapy for stop mutations: How much CFTR activity is enough? Current Opinion in Pulmonary Medicine, 10(6), 547–552. https://doi.org/10.1097/01.mcp.0000141247.22078.46
Kessler,, A. C., Silveira d`Almeida,, G., & Alfonzo,, J. D. (2018). The role of intracellular compartmentalization on tRNA processing and modification. RNA Biology, 15(4–5), 554–566. https://doi.org/10.1080/15476286.2017.1371402
Kirchner,, S., & Ignatova,, Z. (2015). Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nature Reviews. Genetics, 16(2), 98–112. https://doi.org/10.1038/nrg3861
Kiselev,, A. V., Ostapenko,, O. V., Rogozhkina,, E. V., Kholod,, N. S., Seit Nebi,, A. S., Baranov,, A. N., Lesina,, E. A., Ivashchenko,, T. E., Sabetskiĭ,, V. A., Shavlovskiĭ,, M. M., Rechinskiĭ,, V. O., Kiselev,, L. L., & Baranov,, V. C. (2002). Suppression of nonsense mutations in the Dystrophin gene by a suppressor tRNA gene. Molekuliarnaia Biologiia (Mosk), 36(1), 43–47.
Knott,, G. J., & Doudna,, J. A. (2018). CRISPR‐Cas guides the future of genetic engineering. Science, 361(6405), 866–869. https://doi.org/10.1126/science.aat5011
Kohler,, A., & Hurt,, E. (2007). Exporting RNA from the nucleus to the cytoplasm. Nature Reviews. Molecular Cell Biology, 8(10), 761–773. https://doi.org/10.1038/nrm2255
Komor,, A. C., Badran,, A. H., & Liu,, D. R. (2017). CRISPR‐based Technologies for the Manipulation of eukaryotic genomes. Cell, 168(1–2), 20–36. https://doi.org/10.1016/j.cell.2016.10.044
Kotagama,, O. W., Jayasinghe,, C. D., & Abeysinghe,, T. (2019). Era of genomic medicine: A narrative review on CRISPR technology as a potential therapeutic tool for human diseases. BioMed Research International, 2019(1369682), 1–15. https://doi.org/10.1155/2019/1369682
Kowalski,, P. S., Rudra,, A., Miao,, L., & Anderson,, D. G. (2019). Delivering the messenger: Advances in Technologies for Therapeutic mRNA delivery. Molecular Therapy, 27(4), 710–728. https://doi.org/10.1016/j.ymthe.2019.02.012
Kramarski,, L., & Arbely,, E. (2020). Translational read‐through promotes aggregation and shapes stop codon identity. Nucleic Acids Research, 48(7), 3747–3760. https://doi.org/10.1093/nar/gkaa136
Krishnamurthy,, S., Wohlford‐Lenane,, C., Kandimalla,, S., Sartre,, G., Meyerholz,, D. K., Theberge,, V., Théberge,, V., Hallée,, S., Duperré,, A. M., Del`Guidice,, T., Lepetit‐Stoffaes,, J. P., Barbeau,, X., Guay,, D., & McCray,, P. B., Jr. (2019). Engineered amphiphilic peptides enable delivery of proteins and CRISPR‐associated nucleases to airway epithelia. Nature Communications, 10(1), 4906. https://doi.org/10.1038/s41467-019-12922-y
Kubli,, E., Schmidt,, T., Martin,, P. F., & Sofer,, W. (1982). In vitro suppression of a nonsense mutant of Drosophila melanogaster. Nucleic Acids Research, 10(22), 7145–7152. https://doi.org/10.1093/nar/10.22.7145
Kurosaki,, T., Popp,, M. W., & Maquat,, L. E. (2019). Quality and quantity control of gene expression by nonsense‐mediated mRNA decay. Nature Reviews. Molecular Cell Biology, 20(7), 406–420. https://doi.org/10.1038/s41580-019-0126-2
Laski,, F. A., Belagaje,, R., Hudziak,, R. M., Capecchi,, M. R., Norton,, G. P., Palese,, P., RajBhandary,, U. L., & Sharp,, P. A. (1984). Synthesis of an ochre suppressor tRNA gene and expression in mammalian cells. The EMBO Journal, 3(11), 2445–2452.
Ledoux,, S., & Uhlenbeck,, O. C. (2008). Different aa‐tRNAs are selected uniformly on the ribosome. Molecular Cell, 31(1), 114–123. https://doi.org/10.1016/j.molcel.2008.04.026
Lee,, H. L., & Dougherty,, J. P. (2012). Pharmaceutical therapies to recode nonsense mutations in inherited diseases. Pharmacology %26 Therapeutics, 136(2), 227–266. https://doi.org/10.1016/j.pharmthera.2012.07.007
Lehrman,, S. (1999). Virus treatment questioned after gene therapy death. Nature, 401(6753), 517–518. https://doi.org/10.1038/43977
Li,, L., Linning,, R. M., Kondo,, K., & Honda,, B. M. (1998). Differential expression of individual suppressor tRNA(Trp) gene‐gene family members in vitro and in vivo in the nematode Caenorhabditis elegans. Molecular and Cellular Biology, 18(2), 703–709. https://doi.org/10.1128/mcb.18.2.703
Liang,, H., Cavalcanti,, A. R., & Landweber,, L. F. (2005). Conservation of tandem stop codons in yeasts. Genome Biology, 6(4), R31. https://doi.org/10.1186/gb-2005-6-4-r31
Limberis,, M. P., Figueredo,, J., Calcedo,, R., & Wilson,, J. M. (2007). Activation of CFTR‐specific T cells in cystic fibrosis mice following gene transfer. Molecular Therapy, 15(9), 1694–1700. https://doi.org/10.1038/sj.mt.6300210
Linde,, L., Boelz,, S., Nissim‐Rafinia,, M., Oren,, Y. S., Wilschanski,, M., Yaacov,, Y., Virgilis,, D., Neu‐Yilik,, G., Kulozik,, A. E., Kerem,, E., & Kerem,, B. (2007). Nonsense‐mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. The Journal of Clinical Investigation, 117(3), 683–692. https://doi.org/10.1172/JCI28523
Liu,, J., Hemphill,, J., Samanta,, S., Tsang,, M., & Deiters,, A. (2017). Genetic code expansion in Zebrafish embryos and its application to optical control of cell signaling. Journal of the American Chemical Society, 139(27), 9100–9103. https://doi.org/10.1021/jacs.7b02145
Lowe,, T. M., & Eddy,, S. R. (1997). tRNAscan‐SE: A program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Research, 25(5), 955–964. https://doi.org/10.1093/nar/25.5.955
Lueck,, J. D., Yoon,, J. S., Perales‐Puchalt,, A., Mackey,, A. L., Infield,, D. T., Behlke,, M. A., Pope,, M. R., Weiner,, D. B., Skach,, W. R., McCray,, P. B., Jr., & Ahern,, C. A. (2019). Engineered transfer RNAs for suppression of premature termination codons. Nature Communications, 10(1), 822. https://doi.org/10.1038/s41467-019-08329-4
Lukacs,, G. L., Haggie,, P., Seksek,, O., Lechardeur,, D., Freedman,, N., & Verkman,, A. S. (2000). Size‐dependent DNA mobility in cytoplasm and nucleus. The Journal of Biological Chemistry, 275(3), 1625–1629. https://doi.org/10.1074/jbc.275.3.1625
Lundstrom,, K. (2018). Viral vectors in gene therapy. Diseases, 6(2), 1–20. https://doi.org/10.3390/diseases6020042
Lynch,, S. R., & Puglisi,, J. D. (2001). Structural origins of aminoglycoside specificity for prokaryotic ribosomes. Journal of Molecular Biology, 306(5), 1037–1058. https://doi.org/10.1006/jmbi.2000.4420
Maguire,, A. M., Simonelli,, F., Pierce,, E. A., Pugh,, E. N., Jr., Mingozzi,, F., Bennicelli,, J., Banfi,, S., Marshall,, K. A., Testa,, F., Surace,, E. M., Rossi,, S., Lyubarsky,, A., Arruda,, V. R., Konkle,, B., Stone,, E., Sun,, J., Jacobs,, J., Dell`Osso,, L., Hertle,, R., … Bennett,, J. (2008). Safety and efficacy of gene transfer for Leber`s congenital amaurosis. The New England Journal of Medicine, 358(21), 2240–2248. https://doi.org/10.1056/NEJMoa0802315
Makino,, H., Saijo,, T., Ashida,, Y., Kuriki,, H., & Maki,, Y. (1987). Mechanism of action of an antiallergic agent, amlexanox (AA‐673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase. International Archives of Allergy and Applied Immunology, 82(1), 66–71. https://doi.org/10.1159/000234292
Manuvakhova,, M., Keeling,, K., & Bedwell,, D. M. (2000). Aminoglycoside antibiotics mediate context‐dependent suppression of termination codons in a mammalian translation system. RNA, 6(7), 1044–1055. https://doi.org/10.1017/s1355838200000716
Maraia,, R. J., & Lamichhane,, T. N. (2011). 3′ processing of eukaryotic precursor tRNAs. WIREs RNA, 2(3), 362–375. https://doi.org/10.1002/wrna.64
Maywood,, E. S., Elliott,, T. S., Patton,, A. P., Krogager,, T. P., Chesham,, J. E., Ernst,, R. J., Beránek,, V., Brancaccio,, M., Chin,, J. W., & Hastings,, M. H. (2018). Translational switching of Cry1 protein expression confers reversible control of circadian behavior in arrhythmic cry‐deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 115(52), E12388–e12397. https://doi.org/10.1073/pnas.1811438115
McCaughan,, K. K., Brown,, C. M., Dalphin,, M. E., Berry,, M. J., & Tate,, W. P. (1995). Translational termination efficiency in mammals is influenced by the base following the stop codon. Proceedings of the National Academy of Sciences of the United States of America, 92(12), 5431–5435. https://doi.org/10.1073/pnas.92.12.5431
McCown,, P. J., Ruszkowska,, A., Kunkler,, C. N., Breger,, K., Hulewicz,, J. P., Wang,, M. C., Springer,, N. A., & Brown,, J. A. (2020). Naturally occurring modified ribonucleosides. WIREs RNA, 11, e1595. https://doi.org/10.1002/wrna.1595
McIlwain,, D. R., Pan,, Q., Reilly,, P. T., Elia,, A. J., McCracken,, S., Wakeham,, A. C., Itie‐Youten,, A., Blencowe,, B. J., & Mak,, T. W. (2010). Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense‐mediated mRNA decay. Proceedings of the National Academy of Sciences of the United States of America, 107(27), 12186–12191. https://doi.org/10.1073/pnas.1007336107
Medghalchi,, S. M., Frischmeyer,, P. A., Mendell,, J. T., Kelly,, A. G., Lawler,, A. M., & Dietz,, H. C. (2001). Rent1, a trans‐effector of nonsense‐mediated mRNA decay, is essential for mammalian embryonic viability. Human Molecular Genetics, 10(2), 99–105. https://doi.org/10.1093/hmg/10.2.99
Mendell,, J. R., Campbell,, K., Rodino‐Klapac,, L., Sahenk,, Z., Shilling,, C., Lewis,, S., Bowles,, D., Gray,, S., Li,, C., Galloway,, G., Malik,, V., Coley,, B., Clark,, K. R., Li,, J., Xiao,, X., Samulski,, J., McPhee,, S. W., Samulski,, R. J., & Walker,, C. M. (2010). Dystrophin immunity in Duchenne`s muscular dystrophy. The New England Journal of Medicine, 363(15), 1429–1437. https://doi.org/10.1056/NEJMoa1000228
Mendell,, J. R., Rodino‐Klapac,, L. R., Rosales‐Quintero,, X., Kota,, J., Coley,, B. D., Galloway,, G., Craenen,, J. M., Lewis,, S., Malik,, V., Shilling,, C., Byrne,, B. J., Conlon,, T., Campbell,, K. J., Bremer,, W. G., Viollet,, L., Walker,, C. M., Sahenk,, Z., & Clark,, K. R. (2009). Limb‐girdle muscular dystrophy type 2D gene therapy restores alpha‐sarcoglycan and associated proteins. Annals of Neurology, 66(3), 290–297. https://doi.org/10.1002/ana.21732
Mendell,, J. T., & Dietz,, H. C. (2001). When the message goes awry: Disease‐producing mutations that influence mRNA content and performance. Cell, 107(4), 411–414. https://doi.org/10.1016/s0092-8674(01)00583-9
Mieruszynski,, S., Digman,, M. A., Gratton,, E., & Jones,, M. R. (2015). Characterization of exogenous DNA mobility in live cells through fluctuation correlation spectroscopy. Scientific Reports, 5, 13848. https://doi.org/10.1038/srep13848
Morais,, P., Adachi,, H., & Yu,, Y. T. (2020). Suppression of nonsense mutations by new emerging technologies. International Journal of Molecular Sciences, 21(12), 1–14. https://doi.org/10.3390/ijms21124394
Mort,, M., Ivanov,, D., Cooper,, D. N., & Chuzhanova,, N. A. (2008). A meta‐analysis of nonsense mutations causing human genetic disease. Human Mutation, 29(8), 1037–1047. https://doi.org/10.1002/humu.20763
Mukai,, T., Kobayashi,, T., Hino,, N., Yanagisawa,, T., Sakamoto,, K., & Yokoyama,, S. (2008). Adding l‐lysine derivatives to the genetic code of mammalian cells with engineered pyrrolysyl‐tRNA synthetases. Biochemical and Biophysical Research Communications, 371(4), 818–822. https://doi.org/10.1016/j.bbrc.2008.04.164
Negrutskii,, B. S., & El`skaya,, A. V. (1998). Eukaryotic translation elongation factor 1 alpha: Structure, expression, functions, and possible role in aminoacyl‐tRNA channeling. Progress in Nucleic Acid Research and Molecular Biology, 60, 47–78. https://doi.org/10.1016/s0079-6603(08)60889-2
Neri,, M., Torelli,, S., Brown,, S., Ugo,, I., Sabatelli,, P., Merlini,, L., Spitali,, P., Rimessi,, P., Gualandi,, F., Sewry,, C., Ferlini,, A., & Muntoni,, F. (2007). Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human. Neuromuscular Disorders, 17(11–12), 913–918. https://doi.org/10.1016/j.nmd.2007.07.005
Neumann,, H., Wang,, K., Davis,, L., Garcia‐Alai,, M., & Chin,, J. W. (2010). Encoding multiple unnatural amino acids via evolution of a quadruplet‐decoding ribosome. Nature, 464(7287), 441–444. https://doi.org/10.1038/nature08817
Nguyen,, L. S., Kim,, H. G., Rosenfeld,, J. A., Shen,, Y., Gusella,, J. F., Lacassie,, Y., Layman,, L. C., Shaffer,, L. G., & Gecz,, J. (2013). Contribution of copy number variants involving nonsense‐mediated mRNA decay pathway genes to neuro‐developmental disorders. Human Molecular Genetics, 22(9), 1816–1825. https://doi.org/10.1093/hmg/ddt035
Nguyen,, L. S., Wilkinson,, M. F., & Gecz,, J. (2014). Nonsense‐mediated mRNA decay: Inter‐individual variability and human disease. Neuroscience %26 Biobehavioral Reviews, 46(Pt 2), 175–186. https://doi.org/10.1016/j.neubiorev.2013.10.016
Nichols,, J. L. (1970). Nucleotide sequence from the polypeptide chain termination region of the coat protein cistron in bacteriophage R17 RNA. Nature, 225(5228), 147–151. https://doi.org/10.1038/225147a0
Noren,, C. J., Anthony‐Cahill,, S. J., Griffith,, M. C., & Schultz,, P. G. (1989). A general method for site‐specific incorporation of unnatural amino acids into proteins. Science, 244(4901), 182–188. https://doi.org/10.1126/science.2649980
Ohira,, T., & Suzuki,, T. (2011). Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast. Proceedings of the National Academy of Sciences of the United States of America, 108(26), 10502–10507. https://doi.org/10.1073/pnas.1105645108
Olejniczak,, M., Dale,, T., Fahlman,, R. P., & Uhlenbeck,, O. C. (2005). Idiosyncratic tuning of tRNAs to achieve uniform ribosome binding. Nature Structural %26 Molecular Biology, 12(9), 788–793. https://doi.org/10.1038/nsmb978
Oussoren,, E., Keulemans,, J., van Diggelen,, O. P., Oemardien,, L. F., Timmermans,, R. G., van der Ploeg,, A. T., & Ruijter,, G. J. (2013). Residual alpha‐L‐iduronidase activity in fibroblasts of mild to severe Mucopolysaccharidosis type I patients. Molecular Genetics and Metabolism, 109(4), 377–381. https://doi.org/10.1016/j.ymgme.2013.05.016
Panchal,, R. G., Wang,, S., McDermott,, J., & Link,, C. J., Jr. (1999). Partial functional correction of xeroderma pigmentosum group a cells by suppressor tRNA. Human Gene Therapy, 10(13), 2209–2219. https://doi.org/10.1089/10430349950017194
Park,, H. S., Hohn,, M. J., Umehara,, T., Guo,, L. T., Osborne,, E. M., Benner,, J., Noren,, C. J., Rinehart,, J., & Söll,, D. (2011). Expanding the genetic code of Escherichia coli with phosphoserine. Science, 333(6046), 1151–1154. https://doi.org/10.1126/science.1207203
Parrish,, A. R., She,, X., Xiang,, Z., Coin,, I., Shen,, Z., Briggs,, S. P., Dillin,, A., & Wang,, L. (2012). Expanding the genetic code of Caenorhabditis elegans using bacterial aminoacyl‐tRNA synthetase/tRNA pairs. ACS Chemical Biology, 7(7), 1292–1302. https://doi.org/10.1021/cb200542j
Pelham,, H. R. (1978). Leaky UAG termination codon in tobacco mosaic virus RNA. Nature, 272(5652), 469–471. https://doi.org/10.1038/272469a0
Perona,, J. J., & Hadd,, A. (2012). Structural diversity and protein engineering of the aminoacyl‐tRNA synthetases. Biochemistry, 51(44), 8705–8729. https://doi.org/10.1021/bi301180x
Philipson,, L., Andersson,, P., Olshevsky,, U., Weinberg,, R., Baltimore,, D., & Gesteland,, R. (1978). Translation of MuLV and MSV RNAs in nuclease‐treated reticulocyte extracts: Enhancement of the gag‐pol polypeptide with yeast suppressor tRNA. Cell, 13(1), 189–199. https://doi.org/10.1016/0092-8674(78)90149-6
Phizicky,, E. M., & Hopper,, A. K. (2010). tRNA biology charges to the front. Genes %26 Development, 24(17), 1832–1860. https://doi.org/10.1101/gad.1956510
Pilgrim,, D. B., & Bell,, J. B. (1993). Expression of a Drosophila melanogaster amber suppressor tRNA(Ser) in Caenorhabditis elegans. Molecular %26 General Genetics, 241(1–2), 26–32. https://doi.org/10.1007/bf00280197
Popp,, M. W.‐L., & Maquat,, L. E. (2013). Organizing principles of mammalian nonsense‐mediated mRNA decay. Annual Review of Genetics, 47, 139–165.
Qian,, Y., & Guan,, M. X. (2009). Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness‐associated mutation. Antimicrobial Agents and Chemotherapy, 53(11), 4612–4618. https://doi.org/10.1128/AAC.00965-08
Raina,, M., & Ibba,, M. (2014). tRNAs as regulators of biological processes. Frontiers in Genetics, 5, 171. https://doi.org/10.3389/fgene.2014.00171
Ramamoorth,, M., & Narvekar,, A. (2015). Non viral vectors in gene therapy‐ an overview. Journal of Clinical and Diagnostic Research, 9(1), GE01–GE06. https://doi.org/10.7860/JCDR/2015/10443.5394
Rauch,, B. J., Porter,, J. J., Mehl,, R. A., & Perona,, J. J. (2016). Improved incorporation of noncanonical amino acids by an engineered tRNA(Tyr) suppressor. Biochemistry, 55(3), 618–628. https://doi.org/10.1021/acs.biochem.5b01185
Rawlins,, D. R., Collis,, P., & Muzyczka,, N. (1983). Characterization of am404, an amber mutation in the simian virus 40 T antigen gene. Journal of Virology, 47(1), 202–216.
Richard,, P., & Manley,, J. L. (2009). Transcription termination by nuclear RNA polymerases. Genes %26 Development, 23(11), 1247–1269. https://doi.org/10.1101/gad.1792809
Rogerson,, D. T., Sachdeva,, A., Wang,, K., Haq,, T., Kazlauskaite,, A., Hancock,, S. M., Huguenin‐Dezot,, N., Muqit,, M. M. K., Fry,, A. M., Bayliss,, R., & Chin,, J. W. (2015). Efficient genetic encoding of phosphoserine and its nonhydrolyzable analog. Nature Chemical Biology, 11(7), 496–503. https://doi.org/10.1038/nchembio.1823
Sakamoto,, K., Hayashi,, A., Sakamoto,, A., Kiga,, D., Nakayama,, H., Soma,, A., Kobayashi,, T., Kitabatake,, M., Takio,, K., Saito,, K., Shirouzu,, M., Hirao,, I., & Yokoyama,, S. (2002). Site‐specific incorporation of an unnatural amino acid into proteins in mammalian cells. Nucleic Acids Research, 30(21), 4692–4699. https://doi.org/10.1093/nar/gkf589
Sako,, Y., Usuki,, F., & Suga,, H. (2006). A novel therapeutic approach for genetic diseases by introduction of suppressor tRNA. Nucleic Acids Symposium Series, 50, 239–240. https://doi.org/10.1093/nass/nrl119
Saks,, M. E., Sampson,, J. R., Nowak,, M. W., Kearney,, P. C., Du,, F., Abelson,, J. N., Lester,, H. A., & Dougherty,, D. A. (1996). An engineered tetrahymena tRNAGln for in vivo incorporation of unnatural amino acids into proteins by nonsense suppression. The Journal of Biological Chemistry, 271(38), 23169–23175. https://doi.org/10.1074/jbc.271.38.23169
Salvatori,, F., Breveglieri,, G., Zuccato,, C., Finotti,, A., Bianchi,, N., Borgatti,, M., Feriotto,, G., Destro,, F., Canella,, A., Brognara,, E., Lampronti,, I., Breda,, L., Rivella,, S., & Gambari,, R. (2009). Production of beta‐globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous beta(0)39 thalassemia patients. American Journal of Hematology, 84(11), 720–728. https://doi.org/10.1002/ajh.21539
Sambrook,, J. F., Fan,, D. P., & Brenner,, S. (1967). A strong suppressor specific for UGA. Nature, 214(5087), 452–453. https://doi.org/10.1038/214452a0
Sarabhai,, A. S., Stretton,, A. O., Brenner,, S., & Bolle,, A. (1964). Co‐linearity of the gene with the polypeptide chain. Nature, 201, 13–17. https://doi.org/10.1038/201013a0
Schimmel,, P. (2018). The emerging complexity of the tRNA world: Mammalian tRNAs beyond protein synthesis. Nature Reviews. Molecular Cell Biology, 19(1), 45–58. https://doi.org/10.1038/nrm.2017.77
Schmied,, W. H., Elsasser,, S. J., Uttamapinant,, C., & Chin,, J. W. (2014). Efficient multisite unnatural amino acid incorporation in mammalian cells via optimized pyrrolysyl tRNA synthetase/tRNA expression and engineered eRF1. Journal of the American Chemical Society, 136(44), 15577–15583. https://doi.org/10.1021/ja5069728
Schmitt,, M. A., Biddle,, W., & Fisk,, J. D. (2018). Mapping the plasticity of the Escherichia coli genetic code with orthogonal pair‐directed sense codon reassignment. Biochemistry, 57(19), 2762–2774. https://doi.org/10.1021/acs.biochem.8b00177
Schneider,, C., Anderson,, J. T., & Tollervey,, D. (2007). The exosome subunit Rrp44 plays a direct role in RNA substrate recognition. Molecular Cell, 27(2), 324–331. https://doi.org/10.1016/j.molcel.2007.06.006
Schwark,, D. G., Schmitt,, M. A., & Fisk,, J. D. (2018). Dissecting the contribution of release factor interactions to Amber stop codon reassignment efficiencies of the Methanocaldococcus jannaschii orthogonal pair. Genes (Basel), 9(11), 1–17. https://doi.org/10.3390/genes9110546
Serfling,, R., Lorenz,, C., Etzel,, M., Schicht,, G., Bottke,, T., Morl,, M., & Coin,, I. (2018). Designer tRNAs for efficient incorporation of non‐canonical amino acids by the pyrrolysine system in mammalian cells. Nucleic Acids Research, 46(1), 1–10. https://doi.org/10.1093/nar/gkx1156
Shaheen,, H. H., Horetsky,, R. L., Kimball,, S. R., Murthi,, A., Jefferson,, L. S., & Hopper,, A. K. (2007). Retrograde nuclear accumulation of cytoplasmic tRNA in rat hepatoma cells in response to amino acid deprivation. Proceedings of the National Academy of Sciences of the United States of America, 104(21), 8845–8850. https://doi.org/10.1073/pnas.0700765104
Shen,, B., Xiang,, Z., Miller,, B., Louie,, G., Wang,, W., Noel,, J. P., Gage,, F. H., & Wang,, L. (2011). Genetically encoding unnatural amino acids in neural stem cells and optically reporting voltage‐sensitive domain changes in differentiated neurons. Stem Cells, 29(8), 1231–1240. https://doi.org/10.1002/stem.679
Shen,, H., Huang,, X., Min,, J., Le,, S., Wang,, Q., Wang,, X., Dogan,, A. A., Liu,, X., Zhang,, P., Draz,, M. S., & Xiao,, J. (2019). Nanoparticle delivery systems for DNA/RNA and their potential applications in nanomedicine. Current Topics in Medicinal Chemistry, 19(27), 2507–2523. https://doi.org/10.2174/1568026619666191024170212
Shin,, H., Park,, S.‐J., Yim,, Y., Kim,, J., Choi,, C., Won,, C., & Min,, D.‐H. (2018). Recent advances in RNA therapeutics and RNA delivery systems based on nanoparticles. Advanced Therapeutics, 1(7), 1–27. https://doi.org/10.1002/adtp.201800065
Shoemaker,, C. J., & Green,, R. (2012). Translation drives mRNA quality control. Nature Structural %26 Molecular Biology, 19(6), 594–601.
Sicinski,, P., Geng,, Y., Ryder‐Cook,, A. S., Barnard,, E. A., Darlison,, M. G., & Barnard,, P. J. (1989). The molecular basis of muscular dystrophy in the mdx mouse: A point mutation. Science, 244(4912), 1578–1580. https://doi.org/10.1126/science.2662404
Srinivasan,, L., & Gopinathan,, K. P. (2001). Differential expression of individual gene copies from within a tRNA multigene family in the mulberry silkworm Bombyx mori. Insect Molecular Biology, 10(6), 523–530. https://doi.org/10.1046/j.0962-1075.2001.00287.x
Stahl,, F. W. (1995). The amber mutants of phage T4. Genetics, 141(2), 439–442.
Takimoto,, J. K., Adams,, K. L., Xiang,, Z., & Wang,, L. (2009). Improving orthogonal tRNA‐synthetase recognition for efficient unnatural amino acid incorporation and application in mammalian cells. Molecular BioSystems, 5(9), 931–934. https://doi.org/10.1039/b904228h
Tarpey,, P. S., Raymond,, F. L., Nguyen,, L. S., Rodriguez,, J., Hackett,, A., Vandeleur,, L., Smith,, R., Shoubridge,, C., Edkins,, S., Stevens,, C., O`Meara,, S., Tofts,, C., Barthorpe,, S., Buck,, G., Cole,, J., Halliday,, K., Hills,, K., Jones,, D., Mironenko,, T., … Gecz,, J. (2007). Mutations in UPF3B, a member of the nonsense‐mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nature Genetics, 39(9), 1127–1133. https://doi.org/10.1038/ng2100
Tate,, W. P., Poole,, E. S., Horsfield,, J. A., Mannering,, S. A., Brown,, C. M., Moffat,, J. G., Dalphin,, M. E., McCaughan,, K. K., Major,, L. L., & Wilson,, D. N. (1995). Translational termination efficiency in both bacteria and mammals is regulated by the base following the stop codon. Biochemistry and Cell Biology, 73(11–12), 1095–1103. https://doi.org/10.1139/o95-118
Temple,, G. F., Dozy,, A. M., Roy,, K. L., & Kan,, Y. W. (1982). Construction of a functional human suppressor tRNA gene: An approach to gene therapy for beta‐thalassaemia. Nature, 296(5857), 537–540. https://doi.org/10.1038/296537a0
Torres,, A. G., Reina,, O., Stephan‐Otto Attolini,, C., & Ribas de Pouplana,, L. (2019). Differential expression of human tRNA genes drives the abundance of tRNA‐derived fragments. Proceedings of the National Academy of Sciences of the United States of America, 116(17), 8451–8456. https://doi.org/10.1073/pnas.1821120116
Tuite,, M. F., Cox,, B. S., & McLaughlin,, C. S. (1981). An homologous in vitro assay for yeast nonsense suppressors. The Journal of Biological Chemistry, 256(14), 7298–7304.
Tuite,, M. F., Cox,, B. S., & McLaughlin,, C. S. (1983). In vitro nonsense suppression in [psi+] and [psi‐] cell‐free lysates of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America, 80(10), 2824–2828. https://doi.org/10.1073/pnas.80.10.2824
Usuki,, F., Yamashita,, A., Higuchi,, I., Ohnishi,, T., Shiraishi,, T., Osame,, M., & Ohno,, S. (2004). Inhibition of nonsense‐mediated mRNA decay rescues the phenotype in Ullrich`s disease. Annals of Neurology, 55(5), 740–744. https://doi.org/10.1002/ana.20107
Usuki,, F., Yamashita,, A., Kashima,, I., Higuchi,, I., Osame,, M., & Ohno,, S. (2006). Specific inhibition of nonsense‐mediated mRNA decay components, SMG‐1 or Upf1, rescues the phenotype of Ullrich disease fibroblasts. Molecular Therapy, 14(3), 351–360. https://doi.org/10.1016/j.ymthe.2006.04.011
Usuki,, F., Yamashita,, A., Shiraishi,, T., Shiga,, A., Onodera,, O., Higuchi,, I., & Ohno,, S. (2013). Inhibition of SMG‐8, a subunit of SMG‐1 kinase, ameliorates nonsense‐mediated mRNA decay‐exacerbated mutant phenotypes without cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 110(37), 15037–15042. https://doi.org/10.1073/pnas.1300654110
van Haasteren,, J., Li,, J., Scheideler,, O. J., Murthy,, N., & Schaffer,, D. V. (2020). The delivery challenge: Fulfilling the promise of therapeutic genome editing. Nature Biotechnology, 38, 845–855. https://doi.org/10.1038/s41587-020-0565-5
Vanacova,, S., Wolf,, J., Martin,, G., Blank,, D., Dettwiler,, S., Friedlein,, A., Langen,, H., Keith,, G., & Keller,, W. (2005). A new yeast poly(a) polymerase complex involved in RNA quality control. PLoS Biology, 3(6), e189. https://doi.org/10.1371/journal.pbio.0030189
Vogel,, A., Schilling,, O., Spath,, B., & Marchfelder,, A. (2005). The tRNase Z family of proteins: Physiological functions, substrate specificity and structural properties. Biological Chemistry, 386(12), 1253–1264. https://doi.org/10.1515/bc.2005.142
Walker,, S. C., & Engelke,, D. R. (2006). Ribonuclease P: The evolution of an ancient RNA enzyme. Critical Reviews in Biochemistry and Molecular Biology, 41(2), 77–102. https://doi.org/10.1080/10409230600602634
Wang,, L., Brock,, A., Herberich,, B., & Schultz,, P. G. (2001). Expanding the genetic code of Escherichia coli. Science, 292(5516), 498–500. https://doi.org/10.1126/science.1060077
Wang,, Q., & Wang,, L. (2008). New methods enabling efficient incorporation of unnatural amino acids in yeast. Journal of the American Chemical Society, 130(19), 6066–6067. https://doi.org/10.1021/ja800894n
Wang,, W., Czaplinski,, K., Rao,, Y., & Peltz,, S. W. (2001). The role of Upf proteins in modulating the translation read‐through of nonsense‐containing transcripts. The EMBO Journal, 20(4), 880–890. https://doi.org/10.1093/emboj/20.4.880
Wang,, W., Takimoto,, J. K., Louie,, G. V., Baiga,, T. J., Noel,, J. P., Lee,, K. F., Slesinger,, P. A., & Wang,, L. (2007). Genetically encoding unnatural amino acids for cellular and neuronal studies. Nature Neuroscience, 10(8), 1063–1072. https://doi.org/10.1038/nn1932
Wangen,, J. R., & Green,, R. (2020). Stop codon context influences genome‐wide stimulation of termination codon readthrough by aminoglycosides. eLife, 9, e52611. https://doi.org/10.7554/eLife.52611
Welch,, E. M., Barton,, E. R., Zhuo,, J., Tomizawa,, Y., Friesen,, W. J., Trifillis,, P., Paushkin,, S., Patel,, M., Trotta,, C. R., Hwang,, S., Wilde,, R. G., Karp,, G., Takasugi,, J., Chen,, G., Jones,, S., Ren,, H., Moon,, Y. C., Corson,, D., Turpoff,, A. A., … Sweeney,, H. L. (2007). PTC124 targets genetic disorders caused by nonsense mutations. Nature, 447(7140), 87–91. https://doi.org/10.1038/nature05756
Williams,, I., Richardson,, J., Starkey,, A., & Stansfield,, I. (2004). Genome‐wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae. Nucleic Acids Research, 32(22), 6605–6616. https://doi.org/10.1093/nar/gkh1004
Xiao,, H., Chatterjee,, A., Choi,, S. H., Bajjuri,, K. M., Sinha,, S. C., & Schultz,, P. G. (2013). Genetic incorporation of multiple unnatural amino acids into proteins in mammalian cells. Angewandte Chemie International Edition, 52(52), 14080–14083. https://doi.org/10.1002/anie.201308137
Xu,, H., Wang,, Y., Lu,, J., Zhang,, B., Zhang,, Z., Si,, L., Wu,, L., Yao,, T., Zhang,, C., Xiao,, S., Zhang,, L., Xia,, Q., & Zhou,, D. (2016). Re‐exploration of the codon context effect on Amber codon‐guided incorporation of noncanonical amino acids in Escherichia coli by the blue‐white screening assay. ChemBioChem, 17(13), 1250–1256. https://doi.org/10.1002/cbic.201600117
Yoshinaka,, Y., Katoh,, I., Copeland,, T. D., & Oroszlan,, S. (1985). Murine leukemia virus protease is encoded by the gag‐pol gene and is synthesized through suppression of an amber termination codon. Proceedings of the National Academy of Sciences of the United States of America, 82(6), 1618–1622. https://doi.org/10.1073/pnas.82.6.1618
Young,, J. F., Capecchi,, M., Laski,, F. A., RajBhandary,, U. L., Sharp,, P. A., & Palese,, P. (1983). Measurement of suppressor transfer RNA activity. Science, 221(4613), 873–875. https://doi.org/10.1126/science.6308765
Zhang,, G., Lukoszek,, R., Mueller‐Roeber,, B., & Ignatova,, Z. (2011). Different sequence signatures in the upstream regions of plant and animal tRNA genes shape distinct modes of regulation. Nucleic Acids Research, 39(8), 3331–3339. https://doi.org/10.1093/nar/gkq1257
Zheng,, Y., Lewis,, T. L., Jr., Igo,, P., Polleux,, F., & Chatterjee,, A. (2017). Virus‐enabled optimization and delivery of the genetic machinery for efficient unnatural amino acid mutagenesis in mammalian cells and tissues. ACS Synthetic Biology, 6(1), 13–18. https://doi.org/10.1021/acssynbio.6b00092
Zipser,, D. (1967). UGA: A third class of suppressible polar mutants. Journal of Molecular Biology, 29, 441–445.

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

Therapeutic promise of engineered nonsense suppressor tRNAs

Browse by Topic

Access to this WIREs title is by subscription only.

The latest WIREs articles in your inbox