Spliceosomal snRNPs are complex particles that proceed through a fascinating maturation pathway. Several steps of this pathway are closely linked to nuclear non-membrane structures called Cajal bodies. In this review, I summarize the last 20 y of research in this field. I primarily focus on snRNP biogenesis, specifically on the steps that involve Cajal bodies. I also evaluate the contribution of the Cajal body in snRNP quality control and discuss the role of snRNPs in Cajal body formation.

Institute of Molecular Genetics Czech Academy of Sciences Prague Czech Republic

Zobrazit více v PubMed

Li DK, Tisdale S, Lotti F, Pellizzoni L. SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease. Semin Cell Dev Biol 2014; 32:22-9; PMID:24769255; https://doi.org/10.1016/j.semcdb.2014.04.026 PubMed DOI PMC

Matera AG, Wang Z. A day in the life of the spliceosome. Nat Rev Mol Cell Biol 2014; 15:108-21; PMID:24452469; https://doi.org/10.1038/nrm3742 PubMed DOI PMC

Patel SB, Bellini M. The assembly of a spliceosomal small nuclear ribonucleoprotein particle. Nucleic Acids Res 2008; 36:6482-93; PMID:18854356; https://doi.org/10.1093/nar/gkn658 PubMed DOI PMC

Fischer U, Englbrecht C, Chari A. Biogenesis of spliceosomal small nuclear ribonucleoproteins. Wiley Interdiscip Rev RNA 2011; 2:718-31; PMID:21823231; https://doi.org/10.1002/wrna.87 PubMed DOI

Sleeman J. Small nuclear RNAs and mRNAs: linking RNA processing and transport to spinal muscular atrophy. Biochem Soc Trans 2013; 41:871-5; PMID:23863147; https://doi.org/10.1042/BST20120016 PubMed DOI

Mroczek S, Dziembowski A. U6 RNA biogenesis and disease association. Wiley Interdiscip Rev RNA 2013; 4:581-92; PMID:23776162; https://doi.org/10.1002/wrna.1181 PubMed DOI

Hernandez N. Formation of the 3′ end of U1 snRNA is directed by a conserved sequence located downstream of the coding region. EMBO J 1985; 4:1827-37; PMID:2411548 PubMed PMC

Baillat D, Hakimi MA, Naar AM, Shilatifard A, Cooch N, Shiekhattar R. Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell 2005; 123:265-76; PMID:16239144; https://doi.org/10.1016/j.cell.2005.08.019 PubMed DOI

Hallais M, Pontvianne F, Andersen PR, Clerici M, Lener D, Benbahouche Nel H, Gostan T, Vandermoere F, Robert MC, Cusack S, et al.. CBC-ARS2 stimulates 3′-end maturation of multiple RNA families and favors cap-proximal processing. Nat Struct Mol Biol 2013; 20:1358-66; PMID:24270878; https://doi.org/10.1038/nsmb.2720 PubMed DOI

Andersen PR, Domanski M, Kristiansen MS, Storvall H, Ntini E, Verheggen C, Schein A, Bunkenborg J, Poser I, Hallais M, et al.. The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nat Struct Mol Biol 2013; 20:1367-76; PMID:24270879; https://doi.org/10.1038/nsmb.2703 PubMed DOI PMC

Ohno M, Segref A, Bachi A, Wilm M, Mattaj IW. PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation. Cell 2000; 101:187-98; PMID:10786834; https://doi.org/10.1016/S0092-8674(00)80829-6 PubMed DOI

Izumi H, McCloskey A, Shinmyozu K, Ohno M. p54nrb/NonO and PSF promote U snRNA nuclear export by accelerating its export complex assembly. Nucleic Acids Res 2014; 42:3998-4007; PMID:24413662; https://doi.org/10.1093/nar/gkt1365 PubMed DOI PMC

Madore SJ, Wieben ED, Pederson T. Intracellular site of U1 small nuclear RNA processing and ribonucleoprotein assembly. J Cell Biol 1984; 98:188-92; PMID:6200485; https://doi.org/10.1083/jcb.98.1.188 PubMed DOI PMC

Madore SJ, Wieben ED, Kunkel GR, Pederson T. Precursors of U4 small nuclear RNA. J Cell Biol 1984; 99:1140-4; PMID:6206077; https://doi.org/10.1083/jcb.99.3.1140 PubMed DOI PMC

Mouaikel J, Verheggen C, Bertrand E, Tazi J, Bordonne R. Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus. Mol Cell 2002; 9:891-901; PMID:11983179; https://doi.org/10.1016/S1097-2765(02)00484-7 PubMed DOI

Huang Q, Jacobson MR, Pederson T. 3′ processing of human pre-U2 small nuclear RNA: a base-pairing interaction between the 3′ extension of the precursor and an internal region. Mol Cell Biol 1997; 17:7178-85; PMID:9372950; https://doi.org/10.1128/MCB.17.12.7178 PubMed DOI PMC

Yang H, Moss ML, Lund E, Dahlberg JE. Nuclear processing of the 3′-terminal nucleotides of pre-U1 RNA in Xenopus laevis oocytes. Mol Cell Biol 1992; 12:1553-60; PMID:1549111; https://doi.org/10.1128/MCB.12.4.1553 PubMed DOI PMC

Huber J, Cronshagen U, Kadokura M, Marshallsay C, Wada T, Sekine M, Lührmann R. Snurportin1, an m3G-cap-specific nuclear import receptor with a novel domain structure. EMBO J 1998; 17:4114-26; PMID:9670026; https://doi.org/10.1093/emboj/17.14.4114 PubMed DOI PMC

Huber J, Dickmanns A, Luhrmann R. The importin-beta binding domain of snurportin1 is responsible for the Ran- and energy-independent nuclear import of spliceosomal U snRNPs in vitro. J Cell Biol 2002; 156:467-79; PMID:11815630; https://doi.org/10.1083/jcb.200108114 PubMed DOI PMC

Ospina JK, Gonsalvez GB, Bednenko J, Darzynkiewicz E, Gerace L, Matera AG. Cross-talk between snurportin1 subdomains. Mol Biol Cell 2005; 16:4660-71; PMID:16030253; https://doi.org/10.1091/mbc.E05-04-0316 PubMed DOI PMC

Narayanan U, Achsel T, Luhrmann R, Matera AG. Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein. Mol Cell 2004; 16:223-34; PMID:15494309; https://doi.org/10.1016/j.molcel.2004.09.024 PubMed DOI

Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG. SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta. Hum Mol Genet 2002; 11:1785-95; PMID:12095920; https://doi.org/10.1093/hmg/11.15.1785 PubMed DOI PMC

Natalizio AH, Matera AG. Identification and characterization of Drosophila Snurportin reveals a role for the import receptor Moleskin/Importin7 in snRNP biogenesis. Mol Biol Cell 2013; PMID:23885126; https://doi.org/10.1091/mbc.E13-03-0118 PubMed DOI PMC

Darzacq X, Jady 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; 21:2746-56; PMID:12032087; https://doi.org/10.1093/emboj/21.11.2746 PubMed DOI PMC

Romac JM, Graff DH, Keene JD. The U1 small nuclear ribonucleoprotein (snRNP) 70K protein is transported independently of U1 snRNP particles via a nuclear localization signal in the RNA-binding domain. Mol Cell Biol 1994; 14:4662-70; PMID:7516470; https://doi.org/10.1128/MCB.14.7.4662 PubMed DOI PMC

Kambach C, Mattaj IW. Nuclear transport of the U2 snRNP-specific U2B″ protein is mediated by both direct and indirect signalling mechanisms. J Cell Sci 1994; 107(Pt 7):1807-16; PMID:7983149 PubMed

Nesic D, Tanackovic G, Kramer A. A role for Cajal bodies in the final steps of U2 snRNP biogenesis. J Cell Sci 2004; 117:4423-33; PMID:15316075; https://doi.org/10.1242/jcs.01308 PubMed DOI

Bizarro J, Dodre M, Huttin A, Charpentier B, Schlotter F, Branlant C, Verheggen C, Massenet S, Bertrand E. NUFIP and the HSP90/R2TP chaperone bind the SMN complex and facilitate assembly of U4-specific proteins. Nucleic Acids Res 2015; 43:8973-89; PMID:26275778; https://doi.org/10.1093/nar/gkv809 PubMed DOI PMC

Novotny I, Malinova A, Stejskalova E, Mateju D, Klimesova K, Roithova A, Švéda M, Knejzlík Z, Staněk D. SART3-dependent accumulation of incomplete spliceosomal snRNPs in cajal bodies. Cell Rep 2015; 10:429-40; PMID:25600876; https://doi.org/10.1016/j.celrep.2014.12.030 PubMed DOI

Gerbi SA, Borovjagin AV, Odreman FE, Lange TS. U4 snRNA nucleolar localization requires the NHPX/15.5-kD protein binding site but not Sm protein or U6 snRNA association. J Cell Biol 2003; 162:821-32; PMID:12939253; https://doi.org/10.1083/jcb.200301071 PubMed DOI PMC

Klingauf M, Stanek D, Neugebauer KM. Enhancement of U4/U6 small nuclear ribonucleoprotein particle association in Cajal bodies predicted by mathematical modeling. Mol Biol Cell 2006; 17:4972-81; PMID:16987958; https://doi.org/10.1091/mbc.E06-06-0513 PubMed DOI PMC

Boon KL, Grainger RJ, Ehsani P, Barrass JD, Auchynnikava T, Inglehearn CF, Beggs JD. prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nat Struct Mol Biol 2007; 14:1077-83; PMID:17934474; https://doi.org/10.1038/nsmb1303 PubMed DOI PMC

Weber G, Cristao VF, de LAF, Santos KF, Holton N, Rappsilber J, Beggs JD, Wahl MC. Mechanism for Aar2p function as a U5 snRNP assembly factor. Genes Dev 2011; 25:1601-12; PMID:21764848; https://doi.org/10.1101/gad.635911 PubMed DOI PMC

Nguyen TH, Li J, Galej WP, Oshikane H, Newman AJ, Nagai K. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure 2013; 21:910-19; PMID:23727230; https://doi.org/10.1016/j.str.2013.04.017 PubMed DOI PMC

Claudius AK, Romani P, Lamkemeyer T, Jindra M, Uhlirova M. Unexpected role of the steroid-deficiency protein ecdysoneless in pre-mRNA splicing. PLoS Genet 2014; 10:e1004287; PMID:24722212; https://doi.org/10.1371/journal.pgen.1004287 PubMed DOI PMC

Stejskalova E, Stanek D. The splicing factor U1-70K interacts with the SMN complex and is required for nuclear gem integrity. J Cell Sci 2014; 127:3909-15; PMID:25052091; https://doi.org/10.1242/jcs.155838 PubMed DOI

So BR, Wan L, Zhang Z, Li P, Babiash E, Duan J, Younis I, Dreyfuss G. A U1 snRNP-specific assembly pathway reveals the SMN complex as a versatile hub for RNP exchange. Nat Struct Mol Biol 2016; 23:225-30; PMID:26828962; https://doi.org/10.1038/nsmb.3167 PubMed DOI PMC

Yu Y, Chi B, Xia W, Gangopadhyay J, Yamazaki T, Winkelbauer-Hurt ME, Yin S, Eliasse Y, Adams E, Shaw CE, et al.. U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish. Nucleic Acids Res 2015; 43:3208-18; PMID:25735748; https://doi.org/10.1093/nar/gkv157 PubMed DOI PMC

Kramer A, Gruter P, Groning K, Kastner B. Combined biochemical and electron microscopic analyses reveal the architecture of the mammalian U2 snRNP. J Cell Biol 1999; 145:1355-68; PMID:10385517; https://doi.org/10.1083/jcb.145.7.1355 PubMed DOI PMC

Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Luhrmann R. Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein. Embo J 2002; 21:4978-88; PMID:12234937; https://doi.org/10.1093/emboj/cdf480 PubMed DOI PMC

Lund E, Dahlberg JE. Cyclic 2′,3′-phosphates and nontemplated nucleotides at the 3′ end of spliceosomal U6 small nuclear RNA's. Science 1992; 255:327-30; PMID:1549778; https://doi.org/10.1126/science.1549778 PubMed DOI

Trippe R, Guschina E, Hossbach M, Urlaub H, Luhrmann R, Benecke BJ. Identification, cloning, and functional analysis of the human U6 snRNA-specific terminal uridylyl transferase. RNA 2006; 12:1494-504; PMID:16790842; https://doi.org/10.1261/rna.87706 PubMed DOI PMC

Rinke J, Steitz JA. Association of the lupus antigen La with a subset of U6 snRNA molecules. Nucleic Acids Res 1985; 13:2617-29; PMID:2582364; https://doi.org/10.1093/nar/13.7.2617 PubMed DOI PMC

Zaric B, Chami M, Remigy H, Engel A, Ballmer-Hofer K, Winkler FK, Kambach C. Reconstitution of two recombinant LSm protein complexes reveals aspects of their architecture, assembly, and function. J Biol Chem 2005; 280:16066-75; PMID:15711010; https://doi.org/10.1074/jbc.M414481200 PubMed DOI

Novotny I, Podolska K, Blazikova M, Valasek LS, Svoboda P, Stanek D. Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling cellular distribution of Like-Sm proteins. Mol Biol Cell 2012; 23:3776-85; PMID:22875987; https://doi.org/10.1091/mbc.E12-02-0085 PubMed DOI PMC

Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kucinski I, Ginalski K, Dziembowski A. C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3′ end modification. Genes Dev 2012; 26:1911-25; PMID:22899009; https://doi.org/10.1101/gad.193169.112 PubMed DOI PMC

Licht K, Medenbach J, Luhrmann R, Kambach C, Bindereif A. 3′-cyclic phosphorylation of U6 snRNA leads to recruitment of recycling factor p110 through LSm proteins. RNA 2008; 14:1532-8; PMID:18567812; https://doi.org/10.1261/rna.1129608 PubMed DOI PMC

Ganot P, Jady BE, Bortolin ML, Darzacq X, Kiss T. Nucleolar factors direct the 2′-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA. Mol Cell Biol 1999; 19:6906-17; PMID:10490628; https://doi.org/10.1128/MCB.19.10.6906 PubMed DOI PMC

Tycowski KT, You ZH, Graham PJ, Steitz JA. Modification of U6 spliceosomal RNA is guided by other small RNAs. Mol Cell 1998; 2:629-38; PMID:9844635; https://doi.org/10.1016/S1097-2765(00)80161-6 PubMed DOI

Gerbi SA, Lange TS. All Small Nuclear RNAs (snRNAs) of the [U4/U6.U5] Tri-snRNP Localize to Nucleoli; Identification of the Nucleolar Localization Element of U6 snRNA. Mol Biol Cell 2002; 13:3123-37; PMID:12221120; https://doi.org/10.1091/mbc.01-12-0596 PubMed DOI PMC

Stanek D, Neugebauer KM. Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer. J Cell Biol 2004; 166:1015-25; PMID:15452143; https://doi.org/10.1083/jcb.200405160 PubMed DOI PMC

Stanek D, Rader SD, Klingauf M, Neugebauer KM. Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies. J Cell Biol 2003; 160:505-16; PMID:12578909; https://doi.org/10.1083/jcb.200210087 PubMed DOI PMC

Bell M, Schreiner S, Damianov A, Reddy R, Bindereif A. p110, a novel human U6 snRNP protein and U4/U6 snRNP recycling factor. Embo J 2002; 21:2724-35; PMID:12032085; https://doi.org/10.1093/emboj/21.11.2724 PubMed DOI PMC

Ruegger S, Miki TS, Hess D, Grosshans H. The ribonucleotidyl transferase USIP-1 acts with SART3 to promote U6 snRNA recycling. Nucleic Acids Res 2015; 43:3344-57; PMID:25753661; https://doi.org/10.1093/nar/gkv196 PubMed DOI PMC

Achsel T, Brahms H, Kastner B, Bachi A, Wilm M, Luhrmann R. A doughnut-shaped heteromer of human Sm-like proteins binds to the 3′- end of U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro. Embo J 1999; 18:5789-802; PMID:10523320; https://doi.org/10.1093/emboj/18.20.5789 PubMed DOI PMC

Nottrott S, Urlaub H, Luhrmann R. Hierarchical, clustered protein interactions with U4/U6 snRNA: a biochemical role for U4/U6 proteins. Embo J 2002; 21:5527-38; PMID:12374753; https://doi.org/10.1093/emboj/cdf544 PubMed DOI PMC

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; 23:3000-9; PMID:15257298; https://doi.org/10.1038/sj.emboj.7600296 PubMed DOI PMC

Makarova OV, Makarov EM, Liu S, Vornlocher HP, Luhrmann R. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6center dotU5 tri-snRNP formation and pre-mRNA splicing. Embo J 2002; 21:1148-57; PMID:11867543; https://doi.org/10.1093/emboj/21.5.1148 PubMed DOI PMC

Liu S, Mozaffari-Jovin S, Wollenhaupt J, Santos KF, Theuser M, Dunin-Horkawicz S, Fabrizio P, Bujnicki JM, Lührmann R, Wahl MC. A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing. eLife 2015; 4:e07320; PMID:26161500; https://doi.org/10.7554/eLife.07320 PubMed DOI PMC

Liu S, Rauhut R, Vornlocher HP, Luhrmann R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA 2006; 12:1418-30; PMID:16723661; https://doi.org/10.1261/rna.55406 PubMed DOI PMC

Nguyen TH, Galej WP, Bai XC, Savva CG, Newman AJ, Scheres SH, Nagai K. The architecture of the spliceosomal U4/U6.U5 tri-snRNP. Nature 2015; 523:47-52; PMID:26106855; https://doi.org/10.1038/nature14548 PubMed DOI PMC

Agafonov DE, Kastner B, Dybkov O, Hofele RV, Liu WT, Urlaub H, Lührmann R, Stark H. Molecular architecture of the human U4/U6.U5 tri-snRNP. Science 2016; 351:1416-20; PMID:26912367; https://doi.org/10.1126/science.aad2085 PubMed DOI

Benecke H, Luhrmann R, Will CL. The U11/U12 snRNP 65K protein acts as a molecular bridge, binding the U12 snRNA and U11-59K protein. EMBO J 2005; 24:3057-69; PMID:16096647; https://doi.org/10.1038/sj.emboj.7600765 PubMed DOI PMC

Machyna M, Neugebauer KM, Stanek D. Coilin: The first 25 years. RNA Biol 2015; 12:590-6; PMID:25970135; https://doi.org/10.1080/15476286.2015.1034923 PubMed DOI PMC

Carmo-Fonseca M, Pepperkok R, Sproat BS, Ansorge W, Swanson MS, Lamond AI. In vivo detection of snRNP-rich organelles in the nuclei of mammalian cells. Embo J 1991; 10:1863-73; PMID:1710980 PubMed PMC

Matera AG, Ward DC. Nucleoplasmic organization of small nuclear ribonucleoproteins in cultured human cells. J Cell Biol 1993; 121:715-27; PMID:8491767; https://doi.org/10.1083/jcb.121.4.715 PubMed DOI PMC

Walker MP, Tian L, Matera AG. Reduced viability, fertility and fecundity in mice lacking the cajal body marker protein, coilin. PLoS One 2009; 4:e6171; PMID:19587784; https://doi.org/10.1371/journal.pone.0006171 PubMed DOI PMC

Tucker KE, Berciano MT, Jacobs EY, LePage DF, Shpargel KB, Rossire JJ, Chan EK, Lafarga M, Conlon RA, Matera AG. 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; PMID:11470819; https://doi.org/10.1083/jcb.200104083 PubMed DOI PMC

Strzelecka M, Trowitzsch S, Weber G, Luhrmann R, Oates AC, Neugebauer KM. Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis. Nat Struct Mol Biol 2010; 17:403-9; PMID:20357773; https://doi.org/10.1038/nsmb.1783 PubMed DOI

Deryusheva S, Gall JG. Dynamics of coilin in Cajal bodies of the Xenopus germinal vesicle. Proc Natl Acad Sci U S A 2004; 101:4810-4; PMID:15044688; https://doi.org/10.1073/pnas.0401106101 PubMed DOI PMC

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; 17:2942-51; PMID:16624863; https://doi.org/10.1091/mbc.E05-12-1157 PubMed DOI PMC

Kanno T, Lin WD, Fu JL, Wu MT, Yang HW, Lin SS, Matzke AJ, Matzke M. Identification of Coilin Mutants in a Screen for Enhanced Expression of an Alternatively Spliced GFP Reporter Gene in Arabidopsis thaliana. Genetics 2016; PMID:27317682; https://doi.org/10.1534/genetics.116.190751 PubMed DOI PMC

Wang Q, Sawyer IA, Sung MH, Sturgill D, Shevtsov SP, Pegoraro G, Hakim O, Baek S, Hager GL, Dundr M. Cajal bodies are linked to genome conformation. Nat Commun 2016; 7:10966; PMID:26997247; https://doi.org/10.1038/ncomms10966 PubMed DOI PMC

Frey MR, Matera AG. 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; 92:5915-9; PMID:7597053; https://doi.org/10.1073/pnas.92.13.5915 PubMed DOI PMC

Smith KP, Carter KC, Johnson CV, Lawrence JB. U2 and U1 snRNA gene loci associate with coiled bodies. J Cell Biochem 1995; 59:473-85; PMID:8749717; https://doi.org/10.1002/jcb.240590408 PubMed DOI

Jacobs EY, Frey MR, Wu W, Ingledue TC, Gebuhr TC, Gao L, Marzluff WF, Matera AG. 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; 10:1653-63; PMID:10233169; https://doi.org/10.1091/mbc.10.5.1653 PubMed DOI PMC

Frey MR, Bailey AD, Weiner AM, Matera AG. Association of snRNA genes with coiled bodies is mediated by nascent snRNA transcripts. Curr Biol 1999; 9:126-35; PMID:10021385; https://doi.org/10.1016/S0960-9822(99)80066-9 PubMed DOI

Frey MR, Matera AG. RNA-mediated interaction of Cajal bodies and U2 snRNA genes. J Cell Biol 2001; 154:499-509; PMID:11489914; https://doi.org/10.1083/jcb.200105084 PubMed DOI PMC

Dundr M, Ospina JK, Sung MH, 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; 179:1095-103; PMID:18070915; https://doi.org/10.1083/jcb.200710058 PubMed DOI PMC

Broome HJ, Hebert MD. Coilin displays differential affinity for specific RNAs in vivo and is linked to telomerase RNA biogenesis. J Mol Biol 2013; 425:713-24; PMID:23274112; https://doi.org/10.1016/j.jmb.2012.12.014 PubMed DOI PMC

Machyna M, Kehr S, Straube K, Kappei D, Buchholz F, Butter F, Ule J, Hertel J, Stadler P, Neugebauer KM. Global identification of coilin binding partners reveals hundreds of small non-coding RNAs that traffic through Cajal bodies. Mol Cell 2014; 56:389-99; PMID:25514182; https://doi.org/10.1016/j.molcel.2014.10.004 PubMed DOI

Matera AG. Of coiled bodies, gems, and salmon. J Cell Biochem 1998; 70:181-92; PMID:9671224; https://doi.org/10.1002/(SICI)1097-4644(19980801)70:2%3c181::AID-JCB4%3e3.0.CO;2-K PubMed DOI

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; 11:2987-98; PMID:10982395; https://doi.org/10.1091/mbc.11.9.2987 PubMed DOI PMC

Takata H, Nishijima H, Maeshima K, Shibahara K. The integrator complex is required for integrity of Cajal bodies. J Cell Sci 2012; 125:166-75; PMID:22250197; https://doi.org/10.1242/jcs.090837 PubMed DOI

Jodoin JN, Sitaram P, Albrecht TR, May SB, Shboul M, Lee E, Reversade B, Wagner EJ, Lee LA. Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the integrator complex. Mol Biol Cell 2013; 24:2954-65; PMID:23904267; https://doi.org/10.1091/mbc.E13-05-0254 PubMed DOI PMC

Broome HJ, Hebert MD. In vitro RNase and nucleic acid binding activities implicate coilin in U snRNA processing. PLoS One 2012; 7:e36300; PMID:22558428; https://doi.org/10.1371/journal.pone.0036300 PubMed DOI PMC

Boulon S, Verheggen C, Jady 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; 16:777-87; PMID:15574332; https://doi.org/10.1016/j.molcel.2004.11.013 PubMed DOI

Massenet S, Pellizzoni L, Paushkin S, Mattaj IW, Dreyfuss G. The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway. Mol Cell Biol 2002; 22:6533-41; PMID:12192051; https://doi.org/10.1128/MCB.22.18.6533-6541.2002 PubMed DOI PMC

Suzuki T, Izumi H, Ohno M. Cajal body surveillance of U snRNA export complex assembly. J Cell Biol 2010; 190:603-12; PMID:20733056; https://doi.org/10.1083/jcb.201004109 PubMed DOI PMC

Sleeman JE, Lamond AI. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr Biol 1999; 9:1065-74; PMID:10531003; https://doi.org/10.1016/S0960-9822(99)80475-8 PubMed DOI

Xu H, Pillai RS, Azzouz TN, Shpargel KB, Kambach C, Hebert MD, Schümperli D, Matera AG. The C-terminal domain of coilin interacts with Sm proteins and U snRNPs. Chromosoma 2005; 114:155-66; PMID:16003501; https://doi.org/10.1007/s00412-005-0003-y PubMed DOI PMC

Hebert MD, Szymczyk PW, Shpargel KB, Matera AG. Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein. Genes Dev 2001; 15:2720-9; PMID:11641277; https://doi.org/10.1101/gad.908401 PubMed DOI PMC

Jady BE, Darzacq X, Tucker KE, Matera AG, Bertrand E, Kiss T. Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm. Embo J 2003; 22:1878-88; PMID:12682020; https://doi.org/10.1093/emboj/cdg187 PubMed DOI PMC

Deryusheva S, Gall JG. Small Cajal body-specific RNAs of Drosophila function in the absence of Cajal bodies. Mol Biol Cell 2009; 20:5250-9; PMID:19846657; https://doi.org/10.1091/mbc.E09-09-0777 PubMed DOI PMC

Tanackovic G, Kramer A. Human splicing factor SF3a, but not SF1, is essential for pre-mRNA splicing in vivo. Mol Biol Cell 2005; 16:1366-77; PMID:15647371; https://doi.org/10.1091/mbc.E04-11-1034 PubMed DOI PMC

Fabrizio P, Dannenberg J, Dube P, Kastner B, Stark H, Urlaub H, Lührmann R. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol Cell 2009; 36:593-608; PMID:19941820; https://doi.org/10.1016/j.molcel.2009.09.040 PubMed DOI

Schultz A, Nottrott S, Hartmuth K, Luhrmann R. RNA structural requirements for the association of the spliceosomal hPrp31 protein with the U4 and U4atac small nuclear ribonucleoproteins. J Biol Chem 2006; 281:28278-86; PMID:16857676; https://doi.org/10.1074/jbc.M603350200 PubMed DOI

Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, Carlomagno T, Wahl MC. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 2007; 316:115-20; PMID:17412961; https://doi.org/10.1126/science.1137924 PubMed DOI

Makarov EM, Makarova OV, Urlaub H, Gentzel M, Will CL, Wilm M, Lührmann R. Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome. Science 2002; 298:2205-8; PMID:12411573; https://doi.org/10.1126/science.1077783 PubMed DOI

Stanek D, Pridalova-Hnilicova J, Novotny I, Huranova M, Blazikova M, Wen X, Sapra AK, Neugebauer KM. Spliceosomal small nuclear ribonucleoprotein particles repeatedly cycle through Cajal bodies. Mol Biol Cell 2008; 19:2534-43; PMID:18367544; https://doi.org/10.1091/mbc.E07-12-1259 PubMed DOI PMC

Pellizzoni L, Kataoka N, Charroux B, Dreyfuss G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 1998; 95:615-24; PMID:9845364; https://doi.org/10.1016/S0092-8674(00)81632-3 PubMed DOI

Vanacova S, Stefl R. The exosome and RNA quality control in the nucleus. EMBO Rep 2007; 8:651-7; PMID:17603538; https://doi.org/10.1038/sj.embor.7401005 PubMed DOI PMC

Hrossova D, Sikorsky T, Potesil D, Bartosovic M, Pasulka J, Zdrahal Z, Stefl R, Vanacova S. RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3′-end extended forms of snRNAs. Nucleic Acids Res 2015; 43:4236-48; PMID:25852104; https://doi.org/10.1093/nar/gkv240 PubMed DOI PMC

Shukla S, Parker R. Quality control of assembly-defective U1 snRNAs by decapping and 5′-to-3′ exonucleolytic digestion. Proc Natl Acad Sci U S A 2014; 111:E3277-86; PMID:25071210; https://doi.org/10.1073/pnas.1412614111 PubMed DOI PMC

Wersig C, Guddat U, Pieler T, Bindereif A. Assembly and nuclear transport of the U4 and U4/U6 snRNPs. Exp Cell Res 1992; 199:373-7; PMID:1371962; https://doi.org/10.1016/0014-4827(92)90447-G PubMed DOI

Fischer U, Sumpter V, Sekine M, Satoh T, Luhrmann R. Nucleo-cytoplasmic transport of U snRNPs: definition of a nuclear location signal in the Sm core domain that binds a transport receptor independently of the m3G cap. EMBO J 1993; 12:573-83; PMID:7679989 PubMed PMC

Fischer U, Heinrich J, van Zee K, Fanning E, Luhrmann R. Nuclear transport of U1 snRNP in somatic cells: differences in signal requirement compared with Xenopus laevis oocytes. J Cell Biol 1994; 125:971-80; PMID:8195300; https://doi.org/10.1083/jcb.125.5.971 PubMed DOI PMC

Stanek D, Neugebauer KM. The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze. Chromosoma 2006; 115:343-54; PMID:16575476; https://doi.org/10.1007/s00412-006-0056-6 PubMed DOI

Sleeman JE, Ajuh P, Lamond AI. snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN. J Cell Sci 2001; 114:4407-19; PMID:11792806 PubMed

Kaiser TE, Intine RV, Dundr M. De novo formation of a subnuclear body. Science 2008; 322:1713-7; PMID:18948503; https://doi.org/10.1126/science.1165216 PubMed DOI

Makarov V, Rakitina D, Protopopova A, Yaminsky I, Arutiunian A, Love AJ, Taliansky M, Kalinina N. Plant coilin: structural characteristics and RNA-binding properties. PLoS One 2013; 8:e53571; PMID:23320094; https://doi.org/10.1371/journal.pone.0053571 PubMed DOI PMC

Tatomer DC, Terzo E, Curry KP, Salzler H, Sabath I, Zapotoczny G, McKay DJ, Dominski Z, Marzluff WF, Duronio RJ. Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis. J Cell Biol 2016; 213:557-70; PMID:27241916; https://doi.org/10.1083/jcb.201504043 PubMed DOI PMC

Novotny I, Blazikova M, Stanek D, Herman P, Malinsky J. In vivo kinetics of U4/U6.U5 tri-snRNP formation in Cajal bodies. Mol Biol Cell 2011; 22:513-23; PMID:21177826; https://doi.org/10.1091/mbc.E10-07-0560 PubMed DOI PMC

Sawyer IA, Dundr M. Nuclear bodies: Built to boost. J Cell Biol 2016; 213:509-11; PMID:27241912; https://doi.org/10.1083/jcb.201605049 PubMed DOI PMC

The SMN complex drives structural changes in human snRNAs to enable snRNP assembly

BRAT1 links Integrator and defective RNA processing with neurodegeneration

A point mutation in human coilin prevents Cajal body formation

DIS3L2 and LSm proteins are involved in the surveillance of Sm ring-deficient snRNAs

The Sm-core mediates the retention of partially-assembled spliceosomal snRNPs in Cajal bodies until their full maturation

Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones