Cajal bodies: where form meets function

Advanced Review

Martin Machyna, Patricia Heyn, Karla M. Neugebauer

Published Online: Oct 05 2012

DOI: 10.1002/wrna.1139

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Abstract The cell nucleus contains dozens of subcompartments that separate biochemical processes into confined spaces. Cajal bodies (CBs) were discovered more than 100 years ago, but only extensive research in the past decades revealed the surprising complexity of molecular and cellular functions taking place in these structures. Many protein and RNA species are modified and assembled within CBs, which have emerged as a meeting place and factory for ribonucleoprotein (RNP) particles involved in splicing, ribosome biogenesis and telomere maintenance. Recently, a distinct structure near histone gene clusters—the Histone locus body (HLB)—was discovered. Involved in histone mRNA 3′‐end formation, HLBs can share several components with CBs. Whether the appearance of distinct HLBs is simply a matter of altered affinity between these structures or of an alternate mode of CB assembly is unknown. However, both structures share basic assembly properties, in which transcription plays a decisive role in initiation. After this seeding event, additional components associate in random order. This appears to be a widespread mechanism for body assembly. CB assembly encompasses an additional layer of complexity, whereby a set of pre‐existing substructures can be integrated into mature CBs. We propose this as a multi‐seeding model of CB assembly. WIREs RNA 2013, 4:17–34. doi: 10.1002/wrna.1139 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Processing > 3' End Processing RNA Export and Localization > RNA Localization

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Overview of Cajal body (CB) functions in different steps of maturation and assembly of ribonucleoprotein complexes (RNPs). After transcription of pre‐snRNAs (U1, U2, U4, U5) by RNA‐polymerase II, m⁷G caps are loaded with cap‐binding complex (CBC). SnRNAs then enter CBs where PHAX and CRM1 are loaded to form export‐competent RNP complexes. After reaching the cytoplasm, the heptameric Sm‐ring is assembled on snRNAs, m³G is formed and 3′‐ends are trimmed. Snurportin then brings these still immature snRNPs back to nucleus where they move to CBs for modification by scaRNPs and addition of snRNP‐specific proteins. Mature snRNPs then move to the nucleoplasm where splicing occurs. After splicing, snRNPs return to CBs for reassembly into active forms. SnoRNAs and scaRNAs are transcribed by Pol II, either as individual genes or harbored within introns. They mature in CBs by associating with specific proteins and then traffic to the nucleolus to process and modify pre‐rRNA and U6 snRNA. U6 snRNA is transcribed by Pol III and, after modification possibly in the nucleolus, enters CBs to be incorporated into U4/U6.U5 tri‐snRNPs. Telomerase follows a maturation pathway similar to snoRNAs but may leave CBs to elongate chromosomal telomeres.112

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Model of histone locus body (HLB) formation in Drosophila melanogaster. (a) Histone gene cluster locus with transcriptional regulators (FLASH, Mxc), which initially assemble on the locus shortly before activation of transcription. Phosphorylation of Mxc during cell‐cycle progression promotes active histone transcription in (b). Upon active transcription, other components of the HLB assemble on the locus; here, non‐ordered assembly is shown. (c) Fully assembled HLB with the major components.

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Shared components between Cajal bodies (CB) and other known types of nuclear bodies. Many protein and RNA types accumulate within CBs. Some of them have been found also in other nuclear subcompartments either because they are in different functional complexes, or shuttle between the two compartments.

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Models for Cajal body (CB) formation. (a) CB self‐assembly via RNA seed. Upon transcriptional activation of specific loci, nascent RNA nucleates the formation of the body by recruiting specific RNA‐binding protein(s). Later, other proteins are added in non‐ordered fashion to create complete canonical CBs. (b) Self‐assembly via coilin. Each of the different RNA species nucleates its own ‘sub‐Cajal body’ (sub‐CB). Note that there is no known RNA component of gems. Sub‐CBs are then integrated into canonical CBs via binding properties of coilin protein. It is not known whether CB formation occurs by different sub CB‐components coming together simultaneously or whether sub‐CBs are pre‐formed and then fuse together, analogous to lipid droplets fusing and possibly taking advantage of proposed phase transitions.

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References

Cioce, M, Lamond, AI. Cajal bodies: a long history of discovery. Annu Rev Cell Dev Biol 2005, 21:105–131.
Strzelecka, M, Oates, AC, Neugebauer, KM. Dynamic control of Cajal body number during zebrafish embryogenesis. Nucleus (Austin, Tex) 2010, 1:96–108.
Pena, E, Berciano, MT, Fernandez, R, Ojeda, JL, Lafarga, M. Neuronal body size correlates with the number of nucleoli and Cajal bodies, and with the organization of the splicing machinery in rat trigeminal ganglion neurons. J Compar Neurol 2001, 430:250–263.
Spector, DL, Lark, G, Huang, S. Differences in snRNP localization between transformed and nontransformed cells. Mol Biol Cell 1992, 3:555–569.
Tucker, K, Berciano, M, Jacobs, E, LePage, D, Shpargel, K, Rossire, J, Chan, E, Lafarga, M, Conlon, R, Matera, A. Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J Cell Biol 2001, 154:293–307.
Raška, I, Andrade, LE, Ochs, RL, Chan, EK, Chang, CM, Roos, G, Tan, EM. Immunological and ultrastructural studies of the nuclear coiled body with autoimmune antibodies. Exp Cell Res 1991, 195:27–37.
Lemm, I, Girard, C, Kuhn, AN, Watkins, NJ, Schneider, M, Bordonné, R, Lührmann, R. Ongoing U snRNP biogenesis is required for the integrity of Cajal bodies. Mol Biol Cell 2006, 17:3221–3231.
Andrade, L, Chan, EK. Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80‐coilin. J Exp Med 1991, 173:1407–1419.
Gall, J. Cajal bodies: the first 100 years. Annu Rev Cell Dev Biol 2000, 16:273–300.
Tuma, RS, Stolk, JA, Roth, MB. Identification and characterization of a sphere organelle protein. J Cell Biol 1993, 122:767–773.
Kato, M, Han, TW, Xie, S, Shi, K, Du, X, Wu, LC, Mirzaei, H, Goldsmith, EJ, Longgood, J, Pei, J, et al. Cell‐free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 2012, 149:753–767.
Han, TW, Kato, M, Xie, S, Wu, LC, Mirzaei, H, Pei, J, Chen, M, Xie, Y, Allen, J, Xiao, G, et al. Cell‐free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 2012, 149:768–779.
Dundr, M, Hebert, MD, Karpova, TS, Stanek, D, Xu, H, Shpargel, KB, Meier, UT, Neugebauer, KM, Matera, AG, Misteli, T. In vivo kinetics of Cajal body components. J Cell Biol 2004, 164:831–842.
Handwerger, K, Murphy, C, Gall, J. Steady‐state dynamics of Cajal body components in the Xenopus germinal vesicle. J Cell Biol 2003, 160:495–504.
Svetlana Deryusheva, JGG. Dynamics of coilin in Cajal bodies of the Xenopus germinal vesicle. Proc Natl Acad Sci USA 2004, 101:4810–4814.
Handwerger, K, Cordero, J, Gall, J. Cajal bodies, nucleoli, and speckles in the Xenopus oocyte nucleus have a low‐density, sponge‐like structure. Mol Biol Cell 2005, 16:202–211.
Brangwynne, CP, Mitchison, TJ, Hyman, AA. Active liquid‐like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc Natl Acad Sci USA 2011, 108:4334–4339.
Brangwynne, CP, Eckmann, CR, Courson, DS, Rybarska, A, Hoege, C, Gharakhani, J, Jülicher, F, Hyman, AA. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science (New York, NY) 2009, 324:1729–1732.
Monneron, A, Bernhard, W. Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res 1969, 27:266–288.
Hebert, M, Szymczyk, P, Shpargel, K, Matera, A. Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein. Genes Dev 2001, 15:2720–2729.
Hao le, T, Fuller, HR, Lam le, T, Le, TT, Burghes, AH, Morris, GE. Absence of gemin5 from SMN complexes in nuclear Cajal bodies. BMC Cell Biol 2007, 8:28.
Staněk, D, Rader, S, Klingauf, M, Neugebauer, K. Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies. J Cell Biol 2003, 160:505–516.
Mouaikel, J, Narayanan, U, Verheggen, C, Matera, AG, Bertrand, E, Tazi, J, Bordonné, R. Interaction between the small‐nuclear‐RNA cap hypermethylase and the spinal muscular atrophy protein, survival of motor neuron. EMBO Rep 2003, 4:616–622.
Verheggen, C, Lafontaine, DLJ, Samarsky, D, Mouaikel, J, Blanchard, J‐M, Bordonné, R, Bertrand, E. Mammalian and yeast U3 snoRNPs are matured in specific and related nuclear compartments. EMBO J 2002, 21:2736–2745.
Tycowski, K, Shu, M, Kukoyi, A, Steitz, J. A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Mol Cell 2009, 34:47–57.
Mahmoudi, S, Henriksson, S, Weibrecht, I, Smith, S, Söderberg, O, Strömblad, S, Wiman, KG, Farnebo, M. WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies. PLoS Biol 2010, 8:e1000521.
Boulon, S, Verheggen, C, Jády, BE, Girard, C, Pescia, C, Paul, C, Ospina, JK, Kiss, T, Matera, AG, Bordonné, R, et al. PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli. Mol Cell 2004, 16:777–787.
Ospina, JK, Gonsalvez, GB, Bednenko, J, Darzynkiewicz, E, Gerace, L, Matera, AG. Cross‐talk between snurportin1 subdomains. Mol Biol Cell 2005, 16: 4660–4671.
Schaffert, N, Hossbach, M, Heintzmann, R, Achsel, T, Luhrmann, R. RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di‐snRNPs in Cajal bodies. EMBO J 2004, 23:3000–3009.
Nesic, D, Tanackovic, G, Krämer, A. A role for Cajal bodies in the final steps of U2 snRNP biogenesis. J Cell Sci 2004, 117:4423–4433.
van Koningsbruggen, S, Dirks, RW, Mommaas, AM, Onderwater, JJ, Deidda, G, Padberg, GW, Frants, RR, van der Maarel, SM. FRG1P is localised in the nucleolus, Cajal bodies, and speckles. J Med Genet 2004, 41:e46.
Gangwani, L, Mikrut, M, Theroux, S, Sharma, M, Davis, RJ. Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein. Nature Cell Biol 2001, 3:376–383.
Carmo‐Fonseca, M, Pepperkok, R, Carvalho, M, Lamond, A. Transcription‐dependent colocalization of the U1, U2, U4/U6, and U5 snRNPs in coiled bodies. J Cell Biol 1992, 117:1–14.
Xu, H, Hebert, M. A novel EB‐1/AIDA‐1 isoform, AIDA‐1c, interacts with the Cajal body protein coilin. BMC Cell Biol 2005, 6:23.
Meier, UT, Blobel, G. NAP57, a mammalian nucleolar protein with a putative homolog in yeast and bacteria. J Cell Biol 1994, 127:1505–1514.
Raška, I, Ochs, RL, Andrade, LE, Chan, EK, Burlingame, R, Peebles, C, Gruol, D, Tan, EM. Association between the nucleolus and the coiled body. J Struct Biol 1990, 104:120–127.
Pogačić, V, Dragon, F, Filipowicz, W. Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Mol Cell Biol 2000, 20:9028–9040.
Lemos, T, Kobarg, J. CGI‐55 interacts with nuclear proteins and co‐localizes to p80‐coilin positive‐coiled bodies in the nucleus. Cell Biochem Biophys 2006, 44:463–474.
Morgan, G, Doyle, O, Murphy, C, Gall, J. RNA polymerase II in Cajal bodies of amphibian oocytes. J Struct Biol 2000, 129:258–268.
Murphy, C, Wang, Z, Roeder, RG, Gall, JG. RNA polymerase III in Cajal bodies and lampbrush chromosomes of the Xenopus oocyte nucleus. Mol Biol Cell 2002, 13:3466–3476.
Polak, PE, Simone, F, Kaberlein, JJ, Luo, RT, Thirman, MJ. ELL and EAF1 are Cajal body components that are disrupted in MLL‐ELL leukemia. Mol Biol Cell 2003, 14:1517–1528.
Espert, L, Eldin, P, Gongora, C, Bayard, B, Harper, F, Chelbi‐Alix, MK, Bertrand, E, Degols, G, Mechti, N. The exonuclease ISG20 mainly localizes in the nucleolus and the Cajal (Coiled) bodies and is associated with nuclear SMN protein‐containing complexes. J Cell Biochem 2006, 98:1320–1333.
Bucci, S, Giani, L, Mancino, G, Pellegrino, M, Ragghianti, M. TAFII70 protein in Cajal bodies of the amphibian germinal vesicle. Genome/Natl Res Council Canada [Genome/Conseil national de recherches Canada] 2001, 44:1100–1103.
Smith, AJ, Ling, Y, Morgan, GT. Subnuclear localization and Cajal body targeting of transcription elongation factor TFIIS in amphibian oocytes. Mol Biol Cell 2003, 14:1255–1267.
Li, CF, Pontes, O, El‐Shami, M, Henderson, IR, Bernatavichute, YV, Chan, SW‐L, Lagrange, T, Pikaard, CS, Jacobsen, SE. An ARGONAUTE4‐containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana. Cell 2006, 126:93–106.
Bruns, A, van Bergeijk, J, Lorbeer, C, Nolle, A, Jungnickel, J, Grothe, C, Claus, P. Fibroblast growth factor‐2 regulates the stability of nuclear bodies. Proc Natl Acad Sci U S A 2009, 106:12747–12752.
Navascues, J, Bengoechea, R, Tapia, O, Casafont, I, Berciano, M, Lafarga, M. SUMO‐1 transiently localizes to Cajal bodies in mammalian neurons. J Struct Biol 2008, 163:137–146.
Sun, J, Xu, H, Subramony, S, Hebert, M. Interactions between coilin and PIASy partially link Cajal bodies to PML bodies. J Cell Sci 2005, 118:4995–5003.
Kotova, E, Jarnik, M, Tulin, AV. Poly (ADP‐ribose) polymerase 1 is required for protein localization to Cajal body. PLoS Genet 2009, 5:e1000387.
Moorhead, GB, Trinkle‐Mulcahy, L, Ulke‐Lemee, A. Emerging roles of nuclear protein phosphatases. Nature Rev Mol Cell Biol 2007, 8:234–244.
Liu, J, Hebert, M, Ye, Y, Templeton, D, Kung, H, Matera, A. Cell cycle‐dependent localization of the CDK2‐cyclin E complex in Cajal (coiled) bodies. J Cell Sci 2000, 113(Pt 9):1543–1552.
Schulz, S, Chachami, G, Kozaczkiewicz, L, Winter, U, Stankovic‐Valentin, N, Haas, P, Hofmann, K, Urlaub, H, Ovaa, H, Wittbrodt, J, et al. Ubiquitin‐specific protease‐like 1 (USPL1) is a SUMO isopeptidase with essential, non‐catalytic functions. EMBO Rep 2012, 1469–3178.
Liu, J, Murphy, C, Buszczak, M, Clatterbuck, S, Goodman, R, Gall, J. The Drosophila melanogaster Cajal body. J Cell Biol 2006, 172:875–884.
Strzelecka, M, Trowitzsch, S, Weber, G, Lührmann, R, Oates, AC, Neugebauer, KM. Coilin‐dependent snRNP assembly is essential for zebrafish embryogenesis. Nat Struct Mol Biol 2010, 17:403–409.
Collier, S, Pendle, A, Boudonck, K, van Rij, T, Dolan, L, Shaw, P. A distant coilin homologue is required for the formation of cajal bodies in Arabidopsis. Mol Biol Cell 2006, 17:2942–2951.
Bauer, D, Murphy, C, Wu, Z, Wu, C, Gall, J. In vitro assembly of coiled bodies in Xenopus egg extract. Mol Biol Cell 1994, 5:633–644.
Santama, N, Ogg, S, Malekkou, A, Zographos, S, Weis, K, Lamond, A. Characterization of hCINAP, a novel coilin‐interacting protein encoded by a transcript from the transcription factor TAFIID32 locus. J Biol Chem 2005, 280:36429–36441.
Skare, P, Kreivi, J‐P, Bergström, A, Karlsson, R. Profilin I colocalizes with speckles and Cajal bodies: a possible role in pre‐mRNA splicing. Exp Cell Res 2003, 286:12–21.
Zhu, Y, Tomlinson, RL, Lukowiak, AA, Terns, RM, Terns, MP. Telomerase RNA accumulates in Cajal bodies in human cancer cells. Mol Biol Cell 2004, 15:81–90.
Brooksbank, C. Cell cycle‐regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Nat Rev Mol Cell Biol 2000, 1:83.
Barcaroli, D, Dinsdale, D, Neale, M, Bongiorno‐Borbone, L, Ranalli, M, Munarriz, E, Sayan, A, McWilliam, J, Smith, T, Fava, E, et al. FLASH is an essential component of Cajal bodies. Proc Natl Acad Sci U S A 2006, 103:14802–14807.
Abbott, J, Marzluff, WF, Gall, JG. The stem‐loop binding protein (SLBP1) is present in coiled bodies of the Xenopus germinal vesicle. Mol Biol Cell 1999, 10:487–499.
Pillai, RS, Will, CL, Luhrmann, R, Schumperli, D, Müller, B. Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1‐like protein. EMBO J 2001, 20:5470–5479.
Liu, JL, Wu, Z, Nizami, Z, Deryusheva, S, Rajendra, TK, Beumer, KJ, Gao, H, Matera, AG, Carroll, D, Gall, JG. Coilin is essential for Cajal body organization in Drosophila melanogaster. Mol Biol Cell 2009, 20:1661–1670.
Cajal, R. Un sencillo metodo de coloracion selectiva del reticulo protoplasmico y sus efectos en los diversos organos nerviosos de vertebrados e invertebrados. Trab Lab Invest Biol 1903, 2:129–221.
Frey, M, Bailey, A, Weiner, A, Matera, A. Association of snRNA genes with coiled bodies is mediated by nascent snRNA transcripts. Curr Biol 1999, 9:126–135.
Kolowerzo, A, Smolinski, DJ, Bednarska, E. Poly(A) RNA a new component of Cajal bodies. Protoplasma 2009, 236:13–19.
Matera, AG, Ward, DC. Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. J Cell Biol 1993, 121:715–727.
Samarsky, DA, Fournier, MJ, Singer, RH, Bertrand, E. The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization. EMBO J 1998, 17:3747–3757.
Richard, P, Darzacq, X, Bertrand, E, Jády, BE, Verheggen, C, Kiss, T. A common sequence motif determines the Cajal body‐specific localization of box H/ACA scaRNAs. EMBO J 2003, 22:4283–4293.
Jády, BE, Kiss, T. A small nucleolar guide RNA functions both in 2′‐O‐ribose methylation and pseudouridylation of the U5 spliceosomal RNA. EMBO J 2001, 20:541–551.
Darzacq, X, Jády, BE, Verheggen, C, Kiss, AM, Bertrand, E, Kiss, T. Cajal body‐specific small nuclear RNAs: a novel class of 2′‐O‐methylation and pseudouridylation guide RNAs. EMBO J 2002, 21:2746–2756.
Tycowski, KT, Aab, A, Steitz, JA. Guide RNAs with 5′ caps and novel box C/D snoRNA‐like domains for modification of snRNAs in metazoa. Curr Biol 2004, 14:1985–1995.
Kiss, AM, Jády, BE, Darzacq, X, Verheggen, C, Bertrand, E, Kiss, T. A Cajal body‐specific pseudouridylation guide RNA is composed of two box H/ACA snoRNA‐like domains. Nucleic Acids Res 2002, 30:4643–4649.
Kiss, AM, Jády, BE, Bertrand, E, Kiss, T. Human box H/ACA pseudouridylation guide RNA machinery. Mol Cell Biol 2004, 24:5797–5807.
Schattner, P, Barberan‐Soler, S, Lowe, TM. A computational screen for mammalian pseudouridylation guide H/ACA RNAs. RNA 2006, 12:15–25.
Huttenhofer, A, Kiefmann, M, Meier‐Ewert, S, O`Brien, J, Lehrach, H, Bachellerie, JP, Brosius, J. RNomics: an experimental approach that identifies 201 candidates for novel, small, non‐messenger RNAs in mouse. EMBO J 2001, 20:2943–2953.
Vitali, P, Royo, H, Seitz, H, Bachellerie, JP, Hüttenhofer, A, Cavaillé, J. Identification of 13 novel human modification guide RNAs. Nucleic Acids Res 2003, 31:6543–6551.
Gu, AD, Zhou, H, Yu, CH, Qu, LH. A novel experimental approach for systematic identification of box H/ACA snoRNAs from eukaryotes. Nucleic Acids Res 2005, 33:e194.
Frey, M, Matera, A. Coiled bodies contain U7 small nuclear RNA and associate with specific DNA sequences in interphase human cells. Proc Natl Acad Sci U S A 1995, 92:5915–5919.
Wu, CH, Gall, JG. U7 small nuclear RNA in C snurposomes of the Xenopus germinal vesicle. Proc Natl Acad Sci U S A 1993, 90:6257–6259.
Ma, T, Van Tine, BA, Wei, Y, Garrett, MD, Nelson, D, Adams, PD, Wang, J, Qin, J, Chow, LT, Harper, JW. Cell cycle‐regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Genes Dev 2000, 14:2298–2313.
Zhao, J, Kennedy, BK, Lawrence, BD, Barbie, DA, Matera, AG, Fletcher, JA, Harlow, E. NPAT links cyclin E‐Cdk2 to the regulation of replication‐dependent histone gene transcription. Genes Dev 2000, 14:2283–2297.
Ghule, PN, Dominski, Z, Lian, JB, Stein, JL, van Wijnen, AJ, Stein, GS. The subnuclear organization of histone gene regulatory proteins and 3′ end processing factors of normal somatic and embryonic stem cells is compromised in selected human cancer cell types. J Cell Physiol 2009, 220:129–135.
Nizami, ZF, Deryusheva, S, Gall, JG. Cajal bodies and histone locus bodies in Drosophila and Xenopus. Cold Spring Harbor Symp Quant Biol 2010, 75:313–320.
Ghule, PN, Becker, KA, Harper, JW, Lian, JB, Stein, JL, van Wijnen, AJ, Stein, GS. Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells. J Cell Physiol 2007, 213:9–17.
Bongiorno‐Borbone, L, De Cola, A, Vernole, P, Finos, L, Barcaroli, D, Knight, RA, Melino, G, De Laurenzi, V. FLASH and NPAT positive but not Coilin positive Cajal Bodies correlate with cell ploidy. Cell Cycle 2008, 7:2357–2367.
Ghule, PN, Dominski, Z, Yang, XC, Marzluff, WF, Becker, KA, Harper, JW, Lian, JB, Stein, JL, van Wijnen, AJ, Stein, GS. Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells. Proc Natl Acad Sci U S A 2008, 105:16964–16969.
White, AE, Burch, BD, Yang, XC, Gasdaska, PY, Dominski, Z, Marzluff, WF, Duronio, RJ. Drosophila histone locus bodies form by hierarchical recruitment of components. J Cell Biol 2011, 193:677–694.
Burch, BD, Godfrey, AC, Gasdaska, PY, Salzler, HR, Duronio, RJ, Marzluff, WF, Dominski, Z. Interaction between FLASH and Lsm11 is essential for histone pre‐mRNA processing in vivo in Drosophila. RNA 2011, 17:1132–1147.
De Cola, A, Bongiorno‐Borbone, L, Bianchi, E, Barcaroli, D, Carletti, E, Knight, RA, Di Ilio, C, Melino, G, Sette, C, De Laurenzi, V. FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription. Oncogene 2012, 31:573–582.
Narita, T, Yung, TM, Yamamoto, J, Tsuboi, Y, Tanabe, H, Tanaka, K, Yamaguchi, Y, Handa, H. NELF interacts with CBC and participates in 3′ end processing of replication‐dependent histone mRNAs. Mol Cell 2007, 26:349–365.
Isogai, Y, Keles, S, Prestel, M, Hochheimer, A, Tjian, R. Transcription of histone gene cluster by differential core‐promoter factors. Genes Dev 2007, 21:2936–2949.
Yang, XC, Burch, BD, Yan, Y, Marzluff, WF, Dominski, Z. FLASH, a proapoptotic protein involved in activation of caspase‐8, is essential for 3′ end processing of histone pre‐mRNAs. Mol Cell 2009, 36:267–278.
Miele, A, Braastad, CD, Holmes, WF, Mitra, P, Medina, R, Xie, R, Zaidi, SK, Ye, X, Wei, Y, Harper, JW, et al. HiNF‐P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition. Mol Cell Biol 2005, 25:6140–6153.
Lee, MC, Toh, LL, Yaw, LP, Luo, Y. Drosophila octamer elements and Pdm‐1 dictate the coordinated transcription of core histone genes. J Biol Chem 2010, 285:9041–9053.
White, AE, Leslie, ME, Calvi, BR, Marzluff, WF, Duronio, RJ. Developmental and cell cycle regulation of the Drosophila histone locus body. Mol Biol Cell 2007, 18:2491–2502.
Bulchand, S, Menon, SD, George, SE, Chia, W. Muscle wasted: a novel component of the Drosophila histone locus body required for muscle integrity. JCell Sci 2010, 123:2697–2707.
Godfrey, AC, White, AE, Tatomer, DC, Marzluff, WF, Duronio, RJ. The Drosophila U7 snRNP proteins Lsm10 and Lsm11 are required for histone pre‐mRNA processing and play an essential role in development. RNA 2009, 15:1661–1672.
Liu, JL, Buszczak, M, Gall, JG. Nuclear bodies in the Drosophila germinal vesicle. Chromosome ResInt J Mol Supramol Evol Aspects Chromosome Biol 2006, 14:465–475.
Wagner, EJ, Burch, BD, Godfrey, AC, Salzler, HR, Duronio, RJ, Marzluff, WF. A genome‐wide RNA interference screen reveals that variant histones are necessary for replication‐dependent histone pre‐mRNA processing. Mol Cell 2007, 28:692–699.
Wagner, EJ, Ospina, JK, Hu, Y, Dundr, M, Matera, AG, Marzluff, WF. Conserved zinc fingers mediate multiple functions of ZFP100, a U7snRNP associated protein. RNA 2006, 12:1206–1218.
Kiriyama, M, Kobayashi, Y, Saito, M, Ishikawa, F, Yonehara, S. Interaction of FLASH with arsenite resistance protein 2 is involved in cell cycle progression at S phase. Mol Cell Biol 2009, 29:4729–4741.
Zhang, J, Zhang, F, Zheng, X. Depletion of hCINAP by RNA interference causes defects in Cajal body formation, histone transcription, and cell viability. Cell Mol Life Sci 2010, 67:1907–1918.
Rajendra, TK, Praveen, K, Matera, AG. Genetic analysis of nuclear bodies: from nondeterministic chaos to deterministic order. Cold Spring Harb Symp Quant Biol 2011, 75:365–374.
Ye, X, Wei, Y, Nalepa, G, Harper, JW. The cyclin E/Cdk2 substrate p220(NPAT) is required for S‐phase entry, histone gene expression, and Cajal body maintenance in human somatic cells. Mol Cell Biol 2003, 23:8586–8600.
Dundr, M, Misteli, T. Biogenesis of nuclear bodies. Cold Spring Harbor Perspect Biol 2010, 2:a000711.
Shevtsov, SP, Dundr, M. Nucleation of nuclear bodies by RNA. Nature Cell Biol 2011, 13:167–173.
Dundr, M. Seed and grow: a two‐step model for nuclear body biogenesis. J Cell Biol 2011, 193:605–606.
Mao, YS, Zhang, B, Spector, DL. Biogenesis and function of nuclear bodies. Trends Genet 2011, 27:295–306.
Karpen, GH, Schaefer, JE, Laird, CD. A Drosophila rRNA gene located in euchromatin is active in transcription and nucleolus formation. Genes Dev 1988, 2:1745–1763.
Filipowicz, W, Pogačić, V. Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Biol 2002, 14:319–327.
Jacobs, E, Frey, M, Wu, W, Ingledue, T, Gebuhr, T, Gao, L, Marzluff, W, Matera, A. Coiled bodies preferentially associate with U4, U11, and U12 small nuclear RNA genes in interphase HeLa cells but not with U6 and U7 genes. Mol Biol Cell 1999, 10:1653–1663.
Smith, KP, Carter, KC, Johnson, CV, Lawrence, JB. U2 and U1 snRNA gene loci associate with coiled bodies. J Cell Biochem 1995, 59:473–485.
Smith, KP, Lawrence, JB. Interactions of U2 gene loci and their nuclear transcripts with Cajal (coiled) bodies: evidence for PreU2 within Cajal bodies. Mol Biol Cell 2000, 11:2987–2998.
Frey, M, Matera, A. RNA‐mediated interaction of Cajal bodies and U2 snRNA genes. J Cell Biol 2001, 154:499–509.
Suzuki, T, Izumi, H, Ohno, M. Cajal body surveillance of U snRNA export complex assembly. J Cell Biol 2010, 190:603–612.
Sleeman, JE, Lamond, AI. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr Biol 1999, 9:1065–1074.
Jády, B, Darzacq, X, Tucker, K, Matera, A, Bertrand, E, Kiss, T. Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm. EMBO J 2003, 22:1878–1888.
Staněk, D, Neugebauer, K. Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer. J Cell Biol 2004, 166:1015–1025.
Staněk, D, Přidalová‐Hnilicová, J, Novotný, I, Huranová, M, Blažíková, M, Wen, X, Sapra, A, Neugebauer, K. Spliceosomal small nuclear ribonucleoprotein particles repeatedly cycle through Cajal bodies. Mol Biol Cell 2008, 19:2534–2543.
Deryusheva, S, Gall, J. Small Cajal body‐specific RNAs (scaRNAs) of Drosophila function in the absence of Cajal bodies. Mol Biol Cell 2009, 20:5250–5259.
Klingauf, M, Staněk, D, Neugebauer, K. Enhancement of U4/U6 small nuclear ribonucleoprotein particle association in Cajal bodies predicted by mathematical modeling. Mol Biol Cell 2006, 17:4972–4981.
Novotný, I, Blažíková, M, Staněk, D, Herman, P, Malinsky, J. In vivo kinetics of U4/U6bulletU5 tri‐snRNP formation in Cajal Bodies. Mol Biol Cell 2010.
Walker, M, Tian, L, Matera, A. Reduced viability, fertility and fecundity in mice lacking the cajal body marker protein, coilin. PLoS ONE 2009, 4:e6171.
Gao, L, Frey, M, Matera, A. Human genes encoding U3 snRNA associate with coiled bodies in interphase cells and are clustered on chromosome 17p11.2 in a complex inverted repeat structure. Nucleic Acids Res 1997, 25:4740–4747.
Schul, W, Adelaar, B, van Driel, R, de Jong, L. Coiled bodies are predisposed to a spatial association with genes that contain snoRNA sequences in their introns. J Cell Biochem 1999, 75:393–403.
Pradet‐Balade, B, Girard, C, Boulon, S, Paul, C, Azzag, K, Bordonné, R, Bertrand, E, Verheggen, C. CRM1 controls the composition of nucleoplasmic pre‐snoRNA complexes to licence them for nucleolar transport. EMBO J 2011, 30:2205–2218.
Narayanan, A, Speckmann, W, Terns, R, Terns, MP. Role of the box C/D motif in localization of small nucleolar RNAs to coiled bodies and nucleoli. Mol Biol Cell 1999, 10:2131–2147.
Jády, BE, Bertrand, E, Kiss, T. Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body‐specific localization signal. J Cell Biol 2004, 164:647–652.
Theimer, CA, Jády, BE, Chim, N, Richard, P, Breece, KE, Kiss, T, Feigon, J. Structural and functional characterization of human telomerase RNA processing and cajal body localization signals. Mol Cell 2007, 27:869–881.
Lukowiak, AA, Narayanan, A, Li, ZH, Terns, RM, Terns, MP. The snoRNA domain of vertebrate telomerase RNA functions to localize the RNA within the nucleus. RNA 2001, 7:1833–1844.
Venteicher, AS, Abreu, EB, Meng, Z, McCann, KE, Terns, RM, Veenstra, TD, Terns, MP, Artandi, SE. A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 2009, 323:644–648.
Tomlinson, RL, Ziegler, TD, Supakorndej, T, Terns, RM, Terns, MP. Cell cycle‐regulated trafficking of human telomerase to telomeres. Mol Biol Cell 2006, 17:955–965.
Jády, B, Richard, P, Bertrand, E, Kiss, T. Cell cycle‐dependent recruitment of telomerase RNA and Cajal bodies to human telomeres. Mol Biol Cell 2006, 17:944–954.
Cristofari, G, Adolf, E, Reichenbach, P, Sikora, K, Terns, RM, Terns, MP, Lingner, J. Human telomerase RNA accumulation in Cajal bodies facilitates telomerase recruitment to telomeres and telomere elongation. Mol Cell 2007, 27:882–889.
Batista, LFZ, Pech, MF, Zhong, FL, Nguyen, HN, Xie, KT, Zaug, AJ, Crary, SM, Choi, J, Sebastiano, V, Cherry, A, et al. Telomere shortening and loss of self‐renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 2011, 474:399–402.
Tomlinson, RL, Li, J, Culp, BR, Terns, RM, Terns, MP. A Cajal body‐independent pathway for telomerase trafficking in mice. Exp Cell Res 2010, 316:2797–2809.
Platani, M, Goldberg, I, Swedlow, J, Lamond, A. In vivo analysis of Cajal body movement, separation, and joining in live human cells. J Cell Biol 2000, 151:1561–1574.
Platani, M, Goldberg, I, Lamond, AI, Swedlow, JR. Cajal body dynamics and association with chromatin are ATP‐dependent. Nature Cell Biol 2002, 4:502–508.
Andrade, LE, Tan, EM, Chan, EK. Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation. Proc Natl Acad Sci U S A 1993, 90:1947–1951.
Kaiser, TE, Intine, RV, Dundr, M. De novo formation of a subnuclear body. Science (New York, NY) 2008, 322:1713–1717.
Mao, YS, Sunwoo, H, Zhang, B, Spector, DL. Direct visualization of the co‐transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 2011, 13:95–101.
Baltanás, FC, Casafont, I, Weruaga, E, Alonso, JR, Berciano, MT, Lafarga, M. Nucleolar disruption and Cajal body disassembly are nuclear hallmarks of DNA damage‐induced neurodegeneration in Purkinje cells. Brain Pathol (Zurich, Switzerland) 2010.
Shav‐Tal, Y, Blechman, J, Darzacq, X, Montagna, C, Dye, BT, Patton, JG, Singer, RH, Zipori, D. Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. Mol Biol Cell 2005, 16:2395–2413.
Dundr, M, Ospina, JK, Sung, M‐H, John, S, Upender, M, Ried, T, Hager, GL, Matera, AG. Actin‐dependent intranuclear repositioning of an active gene locus in vivo. J Cell Biol 2007, 179:1095–1103.
Matera, AG, Shpargel, KB. Pumping RNA: nuclear bodybuilding along the RNP pipeline. Curr Opin Cell Biol 2006, 18:317–324.
Shpargel, KB, Matera, AG. Gemin proteins are required for efficient assembly of Sm‐class ribonucleoproteins. Proc Natl Acad Sci U S A 2005, 102:17372–17377.
Matera, AG, Izaguire‐Sierra, M, Praveen, K, Rajendra, TK. Nuclear bodies: random aggregates of sticky proteins or crucibles of macromolecular assembly? Dev Cell 2009, 17:639–647.
Girard, C, Neel, H, Bertrand, E, Bordonné, R. Depletion of SMN by RNA interference in HeLa cells induces defects in Cajal body formation. Nucleic Acids Res 2006, 34:2925–2932.
Hebert, M, Shpargel, K, Ospina, J, Tucker, K, Matera, A. Coilin methylation regulates nuclear body formation. Dev Cell 2002, 3:329–337.
Young, P, Le, T, Dunckley, M, Nguyen, T, Burghes, A, Morris, G. Nuclear gems and Cajal (coiled) bodies in fetal tissues: nucleolar distribution of the spinal muscular atrophy protein, SMN. Exp Cell Res 2001, 265:252–261.
Toyota, C, Davis, M, Cosman, A, Hebert, M. Coilin phosphorylation mediates interaction with SMN and SmB`. Chromosoma 2009, 119:205–215.
Hearst, S, Gilder, A, Negi, S, Davis, M, George, E, Whittom, A, Toyota, C, Husedzinovic, A, Gruss, O, Hebert, M. Cajal‐body formation correlates with differential coilin phosphorylation in primary and transformed cell lines. J Cell Sci 2009, 122:1872–1881.

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