Tissue‐specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update)

UPDATE

Clinton C. MacDonald

Published Online: Feb 27 2019

DOI: 10.1002/wrna.1526

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Alternative polyadenylation (APA) is how genes choose different sites for 3′ end formation for mRNAs during transcription. APA often occurs in a tissue‐ or developmental stage‐specific manner that can significantly affect gene activity by changing the protein product generated, the stability of the transcript, its localization within the cell, or its translatability. Despite the important regulatory effects that APA has on tissue‐specific gene expression, only a few examples have been characterized mechanistically. In this 2018 update to our 2010 review, we examine mechanisms for the control of APA and update our understanding of the older mechanisms since 2010. We once postulated the existence of tissue‐specific factors in APA. However, while a few tissue‐specific polyadenylation factors are known, the emerging conclusion is that the majority of APA is accomplished by altering levels of core polyadenylation proteins. Examples of those core proteins include CSTF2, CPSF1, and subunits of mammalian cleavage factor I. But despite support for these mechanisms, no one has yet documented any of these proteins changing in either a tissue‐specific or developmental manner. Given the profound effect that APA can have on gene expression and human health, improved understanding of tissue‐specific APA could lead to numerous advances in gene activity control. This article is categorized under: RNA Processing > 3′ End Processing RNA in Disease and Development > RNA in Development

Core and auxiliary proteins involved in tissue‐specific alternative polyadenylation. The pre‐mRNA (black line) consists of upstream sequence elements (UGUA), the polyadenylation signal (AAUAAA), a cleavage site (arrow), the downstream sequence element (GU/UUU), and the downstream G‐rich element (GGGGG). The core polyadenylation proteins consist of the CPSF proteins, the CstF proteins, and CFI_m (see the text for details), and the template‐independent poly(A) polymerase is indicated. Auxiliary (U2AF, hnRNP F, hnRNP H, hnRNP I) and tissue‐specific (Nova‐1, βCstF‐64, τCstF‐64, ELL2, MBNL1/2, HuR/Elavl1, sex‐lethal, FPA, FY, and FCA) proteins are indicated. It is not entirely clear whether symplekin is a core or an auxiliary polyadenylation protein, but it interacts directly with CstF‐64

[ Normal View | Magnified View ]

Proteins involved in testis and brain alternative polyadenylation. (a) Three forms of CstF‐64 are involved in polyadenylation. βCstF‐64 (middle) is an alternatively spliced variant of CstF‐64 (top) that is expressed in vertebrate neurons. τCstF‐64 (bottom) is an autosomal paralog of CstF‐64 that is expressed in male germ cells and other tissues in mammals. The RNA‐binding domain (RBD), CstF‐77 interaction domain (Hinge), proline‐ and glycine‐rich domain (Pro/Gly), MEARA repeats, and C‐terminal domain (CTD) are indicated. (b) Expression patterns of alternative polyadenylation proteins during spermatogenesis. Top figure shows a timeline of spermatogenesis in mice (~34 days). Cells that undergo mitotic division (spermatogonia), meiosis (spermatocytes), and postmeiotic development (round or elongating spermatids, spermatozoa) are indicated. Expression periods for CstF‐64, τCstF‐64, CPSF‐160, CFI_m25, CFI_m68, and Wdr33/WDR33 are shown in the bottom figure. XY inactivation indicates the period of male sex chromosome inactivation

[ Normal View | Magnified View ]

References

Ainsley,, J. A., Drane,, L., Jacobs,, J., Kittelberger,, K. A., & Reijmers,, L. G. (2014). Functionally diverse dendritic mRNAs rapidly associate with ribosomes following a novel experience. Nature Communications, 5, 4510.
Amara,, S. G., Evans,, R. M., & Rosenfeld,, M. G. (1984). Calcitonin/calcitonin gene‐related peptide transcription unit: Tissue‐specific expression involves selective use of alternative polyadenylation sites. Molecular and Cellular Biology, 4, 2151–2160.
Bao,, J., Vitting‐Seerup,, K., Waage,, J., Tang,, C., Ge,, Y., Porse,, B. T., & Yan,, W. (2016). UPF2‐dependent nonsense‐mediated mRNA decay pathway is essential for spermatogenesis by selectively eliminating longer 3′ UTR transcripts. PLoS Genetics, 12, e1005863.
Batra,, R., Charizanis,, K., Manchanda,, M., Mohan,, A., Li,, M., Finn,, D. J., … Swanson,, M. S. (2014). Loss of MBNL leads to disruption of developmentally regulated alternative polyadenylation in RNA‐mediated disease. Molecular Cell, 56, 311–322.
Chakrabarti,, M., Dinkins,, R. D., & Hunt,, A. G. (2018). Genome‐wide atlas of alternative polyadenylation in the forage legume red clover. Scientific Reports, 8, 11379.
Chan,, S. L., Huppertz,, I., Yao,, C., Weng,, L., Moresco,, J. J., Yates,, J. R., 3rd, … Shi,, Y. (2014). CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3′ processing. Genes %26 Development, 28, 2370–2380.
Chang,, J. W., Yeh,, H. S., & Yong,, J. (2017). Alternative polyadenylation in human diseases. Endocrinology and Metabolism, 32, 413–421.
Charlesworth,, A., Meijer,, H. A., & de Moor,, C. H. (2013). Specificity factors in cytoplasmic polyadenylation. WIREs RNA, 4, 437–461.
Chennathukuzhi,, V. M., Lefrancois,, S., Morales,, C. R., Syed,, V., & Hecht,, N. B. (2001). Elevated levels of the polyadenylation factor CstF 64 enhance formation of the 1kB testis brain RNA‐binding protein (TB‐RBP) mRNA in male germ cells. Molecular Reproduction and Development, 58, 460–469.
Clerici,, M., Faini,, M., Aebersold,, R., & Jinek,, M. (2017). Structural insights into the assembly and polyA signal recognition mechanism of the human CPSF complex. eLife, 6, e33111.
Clerici,, M., Faini,, M., Muckenfuss,, L. M., Aebersold,, R., & Jinek,, M. (2018). Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF complex. Nature Structural %26 Molecular Biology, 25, 135–138.
Curinha,, A., Oliveira Braz,, S., Pereira‐Castro,, I., Cruz,, A., & Moreira,, A. (2014). Implications of polyadenylation in health and disease. Nucleus, 5, 508–519.
Dass,, B., Attaya,, E. N., Wallace,, A. M., & MacDonald,, C. C. (2001). Overexpression of the CstF‐64 and CPSF‐160 polyadenylation protein messenger RNAs in mouse male germ cells. Biology of Reproduction, 64, 1722–1729.
Dass,, B., McMahon,, K. W., Jenkins,, N. A., Gilbert,, D. J., Copeland,, N. G., & MacDonald,, C. C. (2001). The gene for a variant form of the polyadenylation protein CstF‐64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice. Journal of Biological Chemistry, 276, 8044–8050.
Dass,, B., Tardif,, S., Park,, J. Y., Tian,, B., Weitlauf,, H. M., Hess,, R. A., … MacDonald,, C. C. (2007). Loss of polyadenylation protein τCstF‐64 causes spermatogenic defects and male infertility. Proceedings of the National Academy of Sciences of the United States of America, 104, 20374–20379.
De Conti,, L., Baralle,, M., & Buratti,, E. (2017). Neurodegeneration and RNA‐binding proteins. WIREs RNA, 8, e1394.
de Lorenzo,, L., Sorenson,, R., Bailey‐Serres,, J., & Hunt,, A. G. (2017). Noncanonical alternative polyadenylation contributes to gene regulation in response to hypoxia. Plant Cell, 29, 1262–1277.
Derti,, A., Garrett‐Engele,, P., Macisaac,, K. D., Stevens,, R. C., Sriram,, S., Chen,, R., … Babak,, T. (2012). A quantitative atlas of polyadenylation in five mammals. Genome Research, 22, 1173–1183.
Di Giammartino,, D. C., Nishida,, K., & Manley,, J. L. (2011). Mechanisms and consequences of alternative polyadenylation. Molecular Cell, 43, 853–866.
Evsyukova,, I., Bradrick,, S. S., Gregory,, S. G., & Garcia‐Blanco,, M. A. (2013). Cleavage and polyadenylation specificity factor 1 (CPSF1) regulates alternative splicing of interleukin 7 receptor (IL7R) exon 6. RNA, 19, 103–115.
Fanourgakis,, G., Lesche,, M., Akpinar,, M., Dahl,, A., & Jessberger,, R. (2016). Chromatoid body protein TDRD6 supports long 3′ UTR triggered nonsense mediated mRNA decay. PLoS Genetics, 12, e1005857.
Fontes,, M. M., Guvenek,, A., Kawaguchi,, R., Zheng,, D., Huang,, A., Ho,, V. M., … Martin,, K. C. (2017). Activity‐dependent regulation of alternative cleavage and polyadenylation during hippocampal long‐term potentiation. Scientific Reports, 7, 17377.
Fu,, H., Yang,, D., Su,, W., Ma,, L., Shen,, Y., Ji,, G., … Li,, Q. Q. (2016). Genome‐wide dynamics of alternative polyadenylation in rice. Genome Research, 26, 1753–1760.
Fukumitsu,, H., Soumiya,, H., & Furukawa,, S. (2012). Knockdown of pre‐mRNA cleavage factor Im 25 kDa promotes neurite outgrowth. Biochemical and Biophysical Research Communications, 425, 848–853.
Gawande,, B., Robida,, M. D., Rahn,, A., & Singh,, R. (2006). Drosophila sex‐lethal protein mediates polyadenylation switching in the female germline. EMBO Journal, 25, 1263–1272.
Gennarino,, V. A., Alcott,, C. E., Chen,, C. A., Chaudhury,, A., Gillentine,, M. A., Rosenfeld,, J. A., … Zoghbi,, H. Y. (2015). NUDT21‐spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation. eLife, 4, e10782.
Grozdanov,, P. N., Amatullah,, A., Graber,, J. H., & MacDonald,, C. C. (2016). TauCstF‐64 mediates correct mRNA polyadenylation and splicing of activator and repressor isoforms of the cyclic AMP‐responsive element modulator (CREM) in mouse testis. Biology of Reproduction, 94, 34.
Grozdanov,, P. N., Li,, J., Yu,, P., Yan,, W., & MacDonald,, C. C. (2018). Cstf2t regulates expression of histones and histone‐like proteins in male germ cells. Andrology, 6, 605–615.
Grozdanov,, P. N., Masoumzadeh,, E., Latham,, M. P., & MacDonald,, C. C. (2018). The structural basis of CstF‐77 modulation of cleavage and polyadenylation through stimulation of CstF‐64 activity. Nucleic Acids Research, 46(22), 12022–12039.
Harris,, J. C., Martinez,, J. M., Grozdanov,, P. N., Bergeson,, S. E., Grammas,, P., & MacDonald,, C. C. (2016). The Cstf2t polyadenylation gene plays a sex‐specific role in learning behaviors in mice. PLoS One, 11, e0165976.
Hatton,, L. S., Eloranta,, J. J., Figueiredo,, L. M., Takagaki,, Y., Manley,, J. L., & O`Hare,, K. (2000). The Drosophila homologue of the 64 kDa subunit of cleavage stimulation factor interacts with the 77 kDa subunit encoded by the suppressor of forked gene. Nucleic Acids Research, 28, 520–526.
Hornyik,, C., Terzi,, L. C., & Simpson,, G. G. (2010). The Spen family protein FPA controls alternative cleavage and polyadenylation of RNA. Developmental Cell, 18, 203–213.
Hunt,, A. G., Xu,, R., Addepalli,, B., Rao,, S., Forbes,, K. P., Meeks,, L. R., … Li,, Q. Q. (2008). Arabidopsis mRNA polyadenylation machinery: Comprehensive analysis of protein–protein interactions and gene expression profiling. BMC Genomics, 9, 220.
Hwang,, H. W., Park,, C. Y., Goodarzi,, H., Fak,, J. J., Mele,, A., Moore,, M. J., … Darnell,, R. B. (2016). PAPERCLIP identifies MicroRNA targets and a role of CstF64/64tau in promoting non‐canonical poly(A) site usage. Cell Reports, 15, 423–435.
Hwang,, H. W., Saito,, Y., Park,, C. Y., Blachere,, N. E., Tajima,, Y., Fak,, J. J., … Darnell,, R. B. (2017). cTag‐PAPERCLIP reveals alternative polyadenylation promotes cell‐type specific protein diversity and shifts Araf isoforms with microglia activation. Neuron, 95, 1334–1349.
Ito,, S., Sakai,, A., Nomura,, T., Miki,, Y., Ouchida,, M., Sasaki,, J., & Shimizu,, K. (2001). A novel WD40 repeat protein, WDC146, highly expressed during spermatogenesis in a stage‐specific manner. Biochemical and Biophysical Research Communications, 280, 656–663.
Ji,, Z., Lee,, J. Y., Pan,, Z., Jiang,, B., & Tian,, B. (2009). Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proceedings of the National Academy of Sciences of the United States of America, 106, 7028–7033.
Kashiwabara,, S. I., Tsuruta,, S., Yamaoka,, Y., Oyama,, K., Iwazaki,, C., & Baba,, T. (2018). PAPOLB/TPAP regulates spermiogenesis independently of chromatoid body‐associated factors. Journal of Reproduction and Development, 64, 25–31.
Kubo,, T., Wada,, T., Yamaguchi,, Y., Shimizu,, A., & Handa,, H. (2006). Knock‐down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3′‐UTRs. Nucleic Acids Research, 34, 6264–6271.
Lackford,, B., Yao,, C., Charles,, G. M., Weng,, L., Zheng,, X., Choi,, E. A., … Shi,, Y. (2014). Fip1 regulates mRNA alternative polyadenylation to promote stem cell self‐renewal. EMBO Journal, 33, 878–889.
Li,, W., Park,, J. Y., Zheng,, D., Hoque,, M., Yehia,, G., & Tian,, B. (2016). Alternative cleavage and polyadenylation in spermatogenesis connects chromatin regulation with post‐transcriptional control. BMC Biology, 14, 6.
Li,, W., Yeh,, H. J., Shankarling,, G. S., Ji,, Z., Tian,, B., & MacDonald,, C. C. (2012). The τCstF‐64 polyadenylation protein controls genome expression in testis. PLoS One, 7, e48373.
Li,, W., You,, B., Hoque,, M., Zheng,, D., Luo,, W., Ji,, Z., … Tian,, B. (2015). Systematic profiling of poly(A)+ transcripts modulated by core 3′ end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation. PLoS Genetics, 11, e1005166.
Licatalosi,, D. D., Mele,, A., Fak,, J. J., Ule,, J., Kayikci,, M., Chi,, S. W., … Darnell,, R. B. (2008). HITS‐CLIP yields genome‐wide insights into brain alternative RNA processing. Nature, 456, 464–469.
Lin,, Y., Li,, Z., Ozsolak,, F., Kim,, S. W., Arango‐Argoty,, G., Liu,, T. T., … John,, B. (2012). An in‐depth map of polyadenylation sites in cancer. Nucleic Acids Research, 40, 8460–8471.
Liu,, D., Brockman,, J. M., Dass,, B., Hutchins,, L. N., Singh,, P., McCarrey,, J. R., … Graber,, J. H. (2007). Systematic variation in mRNA 3′‐processing signals during mouse spermatogenesis. Nucleic Acids Research, 35, 234–246.
Liu,, F., Marquardt,, S., Lister,, C., Swiezewski,, S., & Dean,, C. (2010). Targeted 3′ processing of antisense transcripts triggers Arabidopsis FLC chromatin silencing. Science, 327, 94–97.
Liu,, X., Freitas,, J., Zheng,, D., Oliveira,, M. S., Hoque,, M., Martins,, T., … Moreira,, A. (2017). Transcription elongation rate has a tissue‐specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster. RNA, 23, 1807–1816.
Lorkovic,, Z. J. (2009). Role of plant RNA‐binding proteins in development, stress response and genome organization. Trends in Plant Science, 14, 229–236.
Luo,, W., Ji,, Z., Pan,, Z., You,, B., Hoque,, M., Li,, W., … Tian,, B. (2013). The conserved intronic cleavage and polyadenylation site of CstF‐77 gene imparts control of 3′ end processing activity through feedback autoregulation and by U1 snRNP. PLoS Genetics, 9, e1003613.
Lutz,, C. S., & Moreira,, A. (2011). Alternative mRNA polyadenylation in eukaryotes: An effective regulator of gene expression. WIREs RNA, 2, 23–31.
MacDonald,, C. C., & Grozdanov,, P. N. (2017). Nonsense in the testis: Multiple roles for nonsense‐mediated decay revealed in male reproduction. Biology of Reproduction, 96, 939–947.
MacDonald,, C. C., & McMahon,, K. W. (2010). Tissue‐specific mechanisms of alternative polyadenylation: Testis, brain, and beyond. WIREs RNA, 1, 494–501.
MacDonald,, C. C., & Redondo,, J.‐L. (2002). Reexamining the polyadenylation signal: Were we wrong about AAUAAA? Molecular and Cellular Endocrinology, 190, 1–8.
Mansfield,, K. D., & Keene,, J. D. (2012). Neuron‐specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation. Nucleic Acids Research, 40, 2734–2746.
Martin,, G., Gruber,, A. R., Keller,, W., & Zavolan,, M. (2012). Genome‐wide analysis of pre‐mRNA 3′ end processing reveals a decisive role of human cleavage factor I in the regulation of 3′ UTR length. Cell Reports, 1, 753–763.
Martincic,, K., Alkan,, S. A., Cheatle,, A., Borghesi,, L., & Milcarek,, C. (2009). Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing. Nature Immunology, 10, 1102–1109.
Martincic,, K., Campbell,, R., Edwalds‐Gilbert,, G., Souan,, L., Lotze,, M. T., & Milcarek,, C. (1998). Increase in the 64‐kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition. Proceedings of the National Academy of Sciences of the United States of America, 95, 11095–11100.
Masamha,, C. P., Xia,, Z., Yang,, J., Albrecht,, T. R., Li,, M., Shyu,, A. B., … Wagner,, E. J. (2014). CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature, 510, 412–416.
McMahon,, K. W., Hirsch,, B. A., & MacDonald,, C. C. (2006). Differences in polyadenylation site choice between somatic and male germ cells. BMC Molecular Biology, 7, 35.
Miura,, P., Shenker,, S., Andreu‐Agullo,, C., Westholm,, J. O., & Lai,, E. C. (2013). Widespread and extensive lengthening of 3′ UTRs in the mammalian brain. Genome Research, 23, 812–825.
Nagaike,, T., Logan,, C., Hotta,, I., Rozenblatt‐Rosen,, O., Meyerson,, M., & Manley,, J. L. (2011). Transcriptional activators enhance polyadenylation of mRNA precursors. Molecular Cell, 41, 409–418.
Nazim,, M., Masuda,, A., Rahman,, M. A., Nasrin,, F., Takeda,, J. I., Ohe,, K., … Ohno,, K. (2016). Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms. Nucleic Acids Research, 45(3), 1455–1468.
Ogorodnikov,, A., Kargapolova,, Y., & Danckwardt,, S. (2016). Processing and transcriptome expansion at the mRNA 3′ end in health and disease: Finding the right end. Pflügers Archiv, 468, 993–1012.
Pan,, Z., Zhang,, H., Hague,, L. K., Lee,, J. Y., Lutz,, C. S., & Tian,, B. (2006). An intronic polyadenylation site in human and mouse CstF‐77 genes suggests an evolutionarily conserved regulatory mechanism. Gene, 366, 325–334.
Perepelitsa‐Belancio,, V., & Deininger,, P. (2003). RNA truncation by premature polyadenylation attenuates human mobile element activity. Nature Genetics, 35, 363–366.
Reyes,, A., & Huber,, W. (2018). Alternative start and termination sites of transcription drive most transcript isoform differences across human tissues. Nucleic Acids Research, 46, 582–592.
Sartini,, B. L., Wang,, H., Wang,, W., Millette,, C. F., & Kilpatrick,, D. L. (2008). Pre‐messenger RNA cleavage factor I (CFIm): Potential role in alternative polyadenylation during spermatogenesis. Biology of Reproduction, 78, 472–482.
Schmid,, R., Grellscheid,, S. N., Ehrmann,, I., Dalgliesh,, C., Danilenko,, M., Paronetto,, M. P., … Elliott,, D. J. (2013). The splicing landscape is globally reprogrammed during male meiosis. Nucleic Acids Research, 41, 10170–10184.
Schonemann,, L., Kuhn,, U., Martin,, G., Schafer,, P., Gruber,, A. R., Keller,, W., … Wahle,, E. (2014). Reconstitution of CPSF active in polyadenylation: Recognition of the polyadenylation signal by WDR33. Genes %26 Development, 28, 2381–2393.
Shankarling,, G. S., Coates,, P. W., Dass,, B., & MacDonald,, C. C. (2009). A family of splice variants of CstF‐64 expressed in vertebrate nervous systems. BMC Molecular Biology, 10, 22.
Shankarling,, G. S., & MacDonald,, C. C. (2013). Polyadenylation site‐specific differences in the activity of the neuronal βCstF‐64 protein in PC‐12 cells. Gene, 529, 220–227.
Shi,, Y. (2012). Alternative polyadenylation: New insights from global analyses. RNA, 18, 2105–2117.
Shum,, E. Y., Jones,, S. H., Shao,, A., Dumdie,, J., Krause,, M. D., Chan,, W. K., … Wilkinson,, M. F. (2016). The antagonistic gene paralogs Upf3a and Upf3b govern nonsense‐mediated RNA decay. Cell, 165, 382–395.
Simonelig,, M., Elliott,, K., Mitchelson,, A., & O`Hare,, K. (1996). Interallelic complementation at the suppressor of forked locus of Drosophila reveals complementation between suppressor of forked proteins mutated in different regions. Genetics, 142, 1225–1235.
Simpson,, G. G., Dijkwel,, P. P., Quesada,, V., Henderson,, I., & Dean,, C. (2003). FY is an RNA 3′ end‐processing factor that interacts with FCA to control the Arabidopsis floral transition. Cell, 113, 777–787.
Singh,, I., Lee,, S. H., Sperling,, A. S., Samur,, M. K., Tai,, Y. T., Fulciniti,, M., … Leslie,, C. S. (2018). Widespread intronic polyadenylation diversifies immune cell transcriptomes. Nature Communications, 9, 1716.
Sun,, K., Li,, X., Chen,, X., Bai,, Y., Zhou,, G., Kokiko‐Cochran,, O. N., … Herjan,, T. (2018). Neuron‐specific HuR‐deficient mice spontaneously develop motor neuron disease. Journal of Immunology, 201, 157–166.
Sun,, Y., Zhang,, Y., Hamilton,, K., Manley,, J. L., Shi,, Y., Walz,, T., & Tong,, L. (2018). Molecular basis for the recognition of the human AAUAAA polyadenylation signal. Proceedings of the National Academy of Sciences of the United States of America, 115, E1419–E1428.
Takagaki,, Y., Seipelt,, R. L., Peterson,, M. L., & Manley,, J. L. (1996). The polyadenylation factor CstF‐64 regulates alternative processing of IgM heavy chain pre‐mRNA during B cell differentiation. Cell, 87, 941–952.
Taliaferro,, J. M., Vidaki,, M., Oliveira,, R., Olson,, S., Zhan,, L., Saxena,, T., … Burge,, C. B. (2016). Distal alternative last exons localize mRNAs to neural projections. Molecular Cell, 61, 821–833.
Terenzio,, M., Koley,, S., Samra,, N., Rishal,, I., Zhao,, Q., Sahoo,, P. K., … Fainzilber,, M. (2018). Locally translated mTOR controls axonal local translation in nerve injury. Science, 359, 1416–1421.
Thomas,, J. D., Sznajder,, L. J., Bardhi,, O., Aslam,, F. N., Anastasiadis,, Z. P., Scotti,, M. M., … Swanson,, M. S. (2017). Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy. Genes %26 Development, 31, 1122–1133.
Tian,, B., & Graber,, J. H. (2012). Signals for pre‐mRNA cleavage and polyadenylation. WIREs RNA, 3, 385–396.
Tian,, B., & Manley,, J. L. (2017). Alternative polyadenylation of mRNA precursors. Nature Reviews Molecular Cell Biology, 18, 18–30.
Ule,, J., Jensen,, K. B., Ruggiu,, M., Mele,, A., Ule,, A., & Darnell,, R. B. (2003). CLIP identifies Nova‐regulated RNA networks in the brain. Science, 302, 1212–1215.
Venkataraman,, K., Brown,, K. M., & Gilmartin,, G. M. (2005). Analysis of a noncanonical poly(A) site reveals a tripartite mechanism for vertebrate poly(A) site recognition. Genes %26 Development, 19, 1315–1327.
Wallace,, A. M., Dass,, B., Ravnik,, S. E., Tonk,, V., Jenkins,, N. A., Gilbert,, D. J., … MacDonald,, C. C. (1999). Two distinct forms of the 64,000 M_r protein of the cleavage stimulation factor are expressed in mouse male germ cells. Proceedings of the National Academy of Sciences of the United States of America, 96, 6763–6768.
Wallace,, A. M., Denison,, T., Attaya,, E. N., & MacDonald,, C. C. (2004). Developmental differences in expression of two forms of the CstF‐64 polyadenylation protein in rat and mouse. Biology of Reproduction, 70, 1080–1087.
Wang,, H., Sartini,, B. L., Millette,, C. F., & Kilpatrick,, D. L. (2006). A developmental switch in transcription factor isoforms during spermatogenesis controlled by alternative messenger RNA 3′‐end formation. Biology of Reproduction, 75, 318–323.
Wang,, P. J. (2004). X chromosomes, retrogenes and their role in male reproduction. Trends in Endocrinology and Metabolism, 15, 79–83.
Wang,, R., Zheng,, D., Yehia,, G., & Tian,, B. (2018). A compendium of conserved cleavage and polyadenylation events in mammalian genes. Genome Research, 28, 1427–1441.
Xia,, Z., Donehower,, L. A., Cooper,, T. A., Neilson,, J. R., Wheeler,, D. A., Wagner,, E. J., & Li,, W. (2014). Dynamic analyses of alternative polyadenylation from RNA‐seq reveal a 3′‐UTR landscape across seven tumour types. Nature Communications, 5, 5274.
Xing,, D., Zhao,, H., & Li,, Q. Q. (2008). Arabidopsis CLP1‐SIMILAR PROTEIN3, an ortholog of human polyadenylation factor CLP1, functions in gametophyte, embryo, and postembryonic development. Plant Physiology, 148, 2059–2069.
Xing,, D., Zhao,, H., Xu,, R., & Li,, Q. Q. (2008). Arabidopsis PCFS4, a homologue of yeast polyadenylation factor Pcf11p, regulates FCA alternative processing and promotes flowering time. Plant Journal, 54, 899–910.
Yao,, C., Biesinger,, J., Wan,, J., Weng,, L., Xing,, Y., Xie,, X., & Shi,, Y. (2012). Transcriptome‐wide analyses of CstF64‐RNA interactions in global regulation of mRNA alternative polyadenylation. Proceedings of the National Academy of Sciences of the United States of America, 109, 18773–18778.
Yao,, C., Choi,, E. A., Weng,, L., Xie,, X., Wan,, J., Xing,, Y., … Shi,, Y. (2013). Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3′ processing. RNA, 19, 1781–1790.
Yoon,, O. K., Hsu,, T. Y., Im,, J. H., & Brem,, R. B. (2012). Genetics and regulatory impact of alternative polyadenylation in human B‐lymphoblastoid cells. PLoS Genetics, 8, e1002882.
Youngblood,, B. A., Grozdanov,, P. N., & MacDonald,, C. C. (2014). CstF‐64 supports pluripotency and regulates cell cycle progression in embryonic stem cells through histone 3′ end processing. Nucleic Acids Research, 42, 8330–8342.
Youngblood,, B. A., & MacDonald,, C. C. (2014). CstF‐64 is necessary for endoderm differentiation resulting in cardiomyocyte defects. Stem Cell Research, 13, 413–421.
Zagore,, L. L., Grabinski,, S. E., Sweet,, T. J., Hannigan,, M. M., Sramkoski,, R. M., Li,, Q., & Licatalosi,, D. D. (2015). RNA binding protein Ptbp2 is essential for male germ cell development. Molecular and Cellular Biology, 35, 4030–4042.
Zhang,, H., Lee,, J. Y., & Tian,, B. (2005). Biased alternative polyadenylation in human tissues. Genome Biology, 6, R100.
Zhou,, H. L., Baraniak,, A. P., & Lou,, H. (2007). Role for Fox‐1/Fox‐2 in mediating the neuronal pathway of calcitonin/calcitonin gene‐related peptide alternative RNA processing. Molecular and Cellular Biology, 27, 830–841.
Zhu,, H., Zhou,, H. L., Hasman,, R. A., & Lou,, H. (2007). Hu proteins regulate polyadenylation by blocking sites containing U‐rich sequences. Journal of Biological Chemistry, 282, 2203–2210.
Zhu,, Y., Wang,, X., Forouzmand,, E., Jeong,, J., Qiao,, F., Sowd,, G. A., … Shi,, Y. (2018). Molecular mechanisms for CFIm‐mediated regulation of mRNA alternative polyadenylation. Molecular Cell, 69, 62–74.

Other Versions

Previous Versions

Tissue‐specific mechanisms of alternative polyadenylation: testis, brain, and beyond
Clinton C. MacDonald,K. Wyatt McMahon
Published Online: July 22 2010
DOI: 10.1002/wrna.29

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

Tissue‐specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update)

Browse by Topic

Access to this WIREs title is by subscription only.

The latest WIREs articles in your inbox