A day in the life of the spliceosome (original) (raw)
Berget, S. M., Moore, C. & Sharp, P. A. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proc. Natl Acad. Sci. USA74, 3171–3175 (1977). ArticleCASPubMedPubMed Central Google Scholar
Chow, L. T., Gelinas, R. E., Broker, T. R. & Roberts, R. J. An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell12, 1–8 (1977). ArticleCASPubMed Google Scholar
Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. Are snRNPs involved in splicing? Nature283, 220–224 (1980). ArticleCASPubMed Google Scholar
Jurica, M. S. & Moore, M. J. Pre-mRNA splicing: awash in a sea of proteins. Mol. Cell12, 5–14 (2003). ArticleCASPubMed Google Scholar
Matera, A. G., Terns, R. M. & Terns, M. P. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nature Rev. Mol. Cell Biol.8, 209–220 (2007). ArticleCAS Google Scholar
Henry, R. W., Mittal, V., Ma, B., Kobayashi, R. & Hernandez, N. SNAP19 mediates the assembly of a functional core promoter complex (SNAPc) shared by RNA polymerases II and III. Genes Dev.12, 2664–2672 (1998). ArticleCASPubMedPubMed Central Google Scholar
Hung, K. H. & Stumph, W. E. Regulation of snRNA gene expression by the Drosophila melanogaster small nuclear RNA activating protein complex (DmSNAPc). Crit. Rev. Biochem. Mol. Biol.46, 11–26 (2011). ArticleCASPubMed Google Scholar
Hernandez, N. & Weiner, A. M. Formation of the 3′ end of U1 snRNA requires compatible snRNA promoter elements. Cell47, 249–258 (1986). ArticleCASPubMed Google Scholar
Egloff, S. et al. The integrator complex recognizes a new double mark on the RNA polymerase II carboxyl-terminal domain. J. Biol. Chem.285, 20564–20569 (2010). ArticleCASPubMedPubMed Central Google Scholar
Egloff, S. et al. Serine-7 of the RNA polymerase II CTD is specifically required for snRNA gene expression. Science318, 1777–1779 (2007). ArticleCASPubMedPubMed Central Google Scholar
Baillat, D. et al. Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. Cell123, 265–276 (2005). Identifies the complex that carries out pre-snRNA 3′-end processing. ArticleCASPubMed Google Scholar
Chen, J. et al. An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3′-end formation. RNA18, 2148–2156 (2012). ArticleCASPubMedPubMed Central Google Scholar
Weiner, A. M. E Pluribus Unum: 3′ end formation of polyadenylated mRNAs, histone mRNAs, and U snRNAs. Mol. Cell20, 168–170 (2005). ArticleCASPubMed Google Scholar
Mandel, C. R. et al. Polyadenylation factor CPSF-73 is the pre-mRNA 3′-end-processing endonuclease. Nature444, 953–956 (2006). ArticleCASPubMed Google Scholar
Ezzeddine, N. et al. A subset of Drosophila integrator proteins is essential for efficient U7 snRNA and spliceosomal snRNA 3′-end formation. Mol. Cell. Biol.31, 328–341 (2011). ArticleCASPubMed Google Scholar
Boon, K. L. et al. prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nature Struct. Mol. Biol.14, 1077–1083 (2007). ArticleCAS Google Scholar
Murphy, M. W., Olson, B. L. & Siliciano, P. G. The yeast splicing factor Prp40p contains functional leucine-rich nuclear export signals that are essential for splicing. Genetics166, 53–65 (2004). ArticleCASPubMedPubMed Central Google Scholar
Tkacz, I. D. et al. Identification of novel snRNA-specific Sm proteins that bind selectively to U2 and U4 snRNAs in Trypanosoma brucei. RNA13, 30–43 (2007). ArticleCASPubMedPubMed Central Google Scholar
Hernandez-Verdun, D., Roussel, P., Thiry, M., Sirri, V. & Lafontaine, D. L. The nucleolus: structure/function relationship in RNA metabolism. Wiley Interdiscip. Rev. RNA1, 415–431 (2010). ArticleCASPubMed Google Scholar
Ohno, M., Segref, A., Kuersten, S. & Mattaj, I. W. Identity elements used in export of mRNAs. Mol. Cell9, 659–671 (2002). ArticleCASPubMed Google Scholar
Fuke, H. & Ohno, M. Role of poly (A) tail as an identity element for mRNA nuclear export. Nucleic Acids Res.36, 1037–1049 (2008). ArticleCASPubMed Google Scholar
McCloskey, A. Taniguchi, I., Shinmyozu, K. & Ohno, M. hnRNP C tetramer measures RNA length to classify RNA polymerase II transcripts for export. Science335, 1643–1646 (2012). First identification of a specific function for the non-shuttling hnRNP C-type proteins in RNA export. ArticleCASPubMed Google Scholar
Izaurralde, E. et al. A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell78, 657–668 (1994). ArticleCASPubMed Google Scholar
Ohno, M., Segref, A., Bachi, A., Wilm, M. & Mattaj, I. W. PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation. Cell101, 187–198 (2000). ArticleCASPubMed Google Scholar
Hallais, M. et al. CBC–ARS2 stimulates 3′-end maturation of multiple RNA families and favors cap-proximal processing. Nature Struct. Mol. Biol.20, 1358–1366 (2013). Shows that Ars2 forms 5′ cap-binding subcomplexes that participate in 3′-end processing of three distinct classes of transcript. ArticleCAS Google Scholar
Fornerod, M., Ohno, M., Yoshida, M. & Mattaj, I. W. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell90, 1051–1060 (1997). ArticleCASPubMed Google Scholar
Smith, K. P. & Lawrence, J. B. Interactions of U2 gene loci and their nuclear transcripts with Cajal (coiled) bodies: evidence for PreU2 within Cajal bodies. Mol. Biol. Cell11, 2987–2998 (2000). ArticleCASPubMedPubMed Central Google Scholar
Boulon, S. et al. PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli. Mol. Cell16, 777–787 (2004). ArticleCASPubMed Google Scholar
Matera, A. G., Izaguire-Sierra, M., Praveen, K. & Rajendra, T. K. Nuclear bodies: random aggregates of sticky proteins or crucibles of macromolecular assembly? Dev. Cell17, 639–647 (2009). ArticleCASPubMedPubMed Central Google Scholar
Kitao, S. et al. A compartmentalized phosphorylation/dephosphorylation system that regulates U snRNA export from the nucleus. Mol. Cell. Biol.28, 487–497 (2008). ArticleCASPubMed Google Scholar
Meister, G., Buhler, D., Pillai, R., Lottspeich, F. & Fischer, U. A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nature Cell Biol.3, 945–949 (2001). ArticleCASPubMed Google Scholar
Pellizzoni, L., Yong, J. & Dreyfuss, G. Essential role for the SMN complex in the specificity of snRNP assembly. Science298, 1775–1779 (2002). ArticleCASPubMed Google Scholar
Massenet, S., Pellizzoni, L., Paushkin, S., Mattaj, I. W. & Dreyfuss, G. The SMN complex is associated with snRNPs throughout their cytoplasmic assembly pathway. Mol. Cell. Biol.22, 6533–6541 (2002). ArticleCASPubMedPubMed Central Google Scholar
Narayanan, U., Ospina, J. K., Frey, M. R., Hebert, M. D. & Matera, A. G. SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin β. Hum. Mol. Genet.11, 1785–1795 (2002). ArticleCASPubMed Google Scholar
Mouaikel, J. et al. Interaction between the small-nuclear-RNA cap hypermethylase and the spinal muscular atrophy protein, survival of motor neuron. EMBO Rep.4, 616–622 (2003). ArticleCASPubMedPubMed Central Google Scholar
Meister, G. et al. Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Curr. Biol.11, 1990–1994 (2001). ArticleCASPubMed Google Scholar
Friesen, W. J. et al. The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins. Mol. Cell. Biol.21, 8289–8300 (2001). ArticleCASPubMedPubMed Central Google Scholar
Grimm, C. et al. Structural basis of assembly chaperone-mediated snRNP formation. Mol. Cell49, 692–703 (2013). ArticleCASPubMed Google Scholar
Chari, A. et al. An assembly chaperone collaborates with the SMN complex to generate spliceosomal snRNPs. Cell135, 497–509 (2008). ArticleCASPubMed Google Scholar
Yong, J., Kasim, M., Bachorik, J. L., Wan, L. & Dreyfuss, G. Gemin5 delivers snRNA precursors to the SMN complex for snRNP biogenesis. Mol. Cell38, 551–562 (2010). ArticleCASPubMedPubMed Central Google Scholar
Raker, V. A., Plessel, G. & Luhrmann, R. The snRNP core assembly pathway: identification of stable core protein heteromeric complexes and an snRNP subcore particle in vitro. EMBO J.15, 2256–2269 (1996). ArticleCASPubMedPubMed Central Google Scholar
Kambach, C. et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell96, 375–387 (1999). ArticleCASPubMed Google Scholar
Leung, A. K., Nagai, K. & Li, J. Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature473, 536–539 (2011). Co-crystal structure of U4 snRNA construct with an Sm core definitively shows that the RNA passes through the hole in the Sm ring. ArticleCASPubMedPubMed Central Google Scholar
Kroiss, M. et al. Evolution of an RNP assembly system: a minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster. Proc. Natl Acad. Sci. USA105, 10045–10050 (2008). Shows that both human and fruitfly SMN–GEMIN2 heterodimers are sufficient for mediating Sm core assemblyin vitro. ArticleCASPubMedPubMed Central Google Scholar
Zhang, R. et al. Structure of a key intermediate of the SMN complex reveals Gemin2's crucial function in snRNP assembly. Cell146, 384–395 (2011). Together with reference 46, these papers identify key intermediates in the Sm core assembly pathway, highlighting an unexpected role for GEMIN2. ArticleCASPubMedPubMed Central Google Scholar
Liu, Q., Fischer, U., Wang, F. & Dreyfuss, G. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell90, 1013–1021 (1997). ArticleCASPubMed Google Scholar
Buhler, D., Raker, V., Luhrmann, R. & Fischer, U. Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum. Mol. Genet.8, 2351–2357 (1999). ArticleCASPubMed Google Scholar
Pellizzoni, L., Charroux, B. & Dreyfuss, G. SMN mutants of spinal muscular atrophy patients are defective in binding to snRNP proteins. Proc. Natl Acad. Sci. USA96, 11167–11172 (1999). ArticleCASPubMedPubMed Central Google Scholar
Hannus, S., Buhler, D., Romano, M., Seraphin, B. & Fischer, U. The Schizosaccharomyces pombe protein Yab8p and a novel factor, Yip1p, share structural and functional similarity with the spinal muscular atrophy-associated proteins SMN and SIP1. Hum. Mol. Genet.9, 663–674 (2000). ArticleCASPubMed Google Scholar
Rajendra, T. K. et al. A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. J. Cell Biol.176, 831–841 (2007). ArticleCASPubMedPubMed Central Google Scholar
Shpargel, K. B. & Matera, A. G. Gemin proteins are required for efficient assembly of Sm-class ribonucleoproteins. Proc. Natl Acad. Sci. USA102, 17372–17377 (2005). Assays individual Gemins, as well as a panel of SMN missense mutants for ability to carry out Sm core assembly, showing that certain SMA-causing alleles are functional, whereas others are not. ArticleCASPubMedPubMed Central Google Scholar
Selenko, P. et al. SMN Tudor domain structure and its interaction with the Sm proteins. Nature Struct. Biol.8, 27–31 (2001). ArticleCASPubMed Google Scholar
Lorson, C. L. et al. SMN oligomerization defect correlates with spinal muscular atrophy severity. Nature Genet.19, 63–66 (1998). ArticleCASPubMed Google Scholar
Martin, R., Gupta, K., Ninan, N. S., Perry, K. & Van Duyne, G. D. The survival motor neuron protein forms soluble glycine zipper oligomers. Structure20, 1929–1939 (2012). ArticleCASPubMedPubMed Central Google Scholar
Fischer, U. & Luhrmann, R. An essential signaling role for the m3G cap in the transport of U1 snRNP to the nucleus. Science249, 786–790 (1990). ArticleCASPubMed Google Scholar
Narayanan, U., Achsel, T., Luhrmann, R. & Matera, A. G. Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein. Mol. Cell16, 223–234 (2004). ArticleCASPubMed Google Scholar
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.12, 573–583 (1993). ArticleCASPubMedPubMed Central Google Scholar
Fischer, U., Liu, Q. & Dreyfuss, G. The SMN–SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell90, 1023–1029 (1997). ArticleCASPubMed Google Scholar
Neubauer, G. et al. Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex. Nature Genet.20, 46–50 (1998). ArticleCASPubMed Google Scholar
Trinkle-Mulcahy, L. et al. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes. J. Cell Biol.183, 223–239 (2008). ArticleCASPubMedPubMed Central Google Scholar
Herold, N. et al. Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes. Mol. Cell. Biol.29, 281–301 (2009). ArticleCASPubMed Google Scholar
Matera, A. G. & Shpargel, K. B. Pumping RNA: nuclear bodybuilding along the RNP pipeline. Curr. Opin. Cell Biol.18, 317–324 (2006). ArticleCASPubMed Google Scholar
Stanek, D. & Neugebauer, K. M. The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze. Chromosoma115, 343–354 (2006). ArticleCASPubMed Google Scholar
Sleeman, J. E. & Lamond, A. I. Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway. Curr. Biol.9, 1065–1074 (1999). ArticleCASPubMed Google Scholar
Lamond, A. I. & Spector, D. L. Nuclear speckles: a model for nuclear organelles. Nature Rev. Mol. Cell Biol.4, 605–612 (2003). ArticleCAS Google Scholar
Jady, B. E. et al. Modification of Sm small nuclear RNAs occurs in the nucleoplasmic Cajal body following import from the cytoplasm. EMBO J.22, 1878–1888 (2003). ArticleCASPubMedPubMed Central Google Scholar
Nesic, D., Tanackovic, G. & Kramer, A. A role for Cajal bodies in the final steps of U2 snRNP biogenesis. J. Cell Sci.117, 4423–4433 (2004). ArticleCASPubMed Google Scholar
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.23, 3000–3009 (2004). ArticleCASPubMedPubMed Central Google Scholar
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. Cell22, 513–523 (2011). ArticleCASPubMedPubMed Central Google Scholar
Stanek, D. & Neugebauer, K. M. Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer. J. Cell Biol.166, 1015–1025 (2004). ArticleCASPubMedPubMed Central Google Scholar
Stanek, D., Rader, S. D., Klingauf, M. & Neugebauer, K. M. Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies. J. Cell Biol.160, 505–516 (2003). ArticleCASPubMedPubMed Central Google Scholar
Strzelecka, M., Oates, A. C. & Neugebauer, K. M. Dynamic control of Cajal body number during zebrafish embryogenesis. Nucleus1, 96–108 (2010). ArticlePubMedPubMed Central Google Scholar
Takata, H., Nishijima, H., Maeshima, K. & Shibahara, K. The integrator complex is required for integrity of Cajal bodies. J. Cell Sci.125, 166–175 (2012). ArticleCASPubMed Google Scholar
Tucker, K. E. et al. Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J. Cell Biol.154, 293–307 (2001). ArticleCASPubMedPubMed Central Google Scholar
Walker, M. P., Tian, L. & Matera, A. G. Reduced viability, fertility and fecundity in mice lacking the cajal body marker protein, coilin. PLoS ONE4, e6171 (2009). ArticlePubMedPubMed CentralCAS Google Scholar
Strzelecka, M. et al. Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis. Nature Struct. Mol. Biol.17, 403–409 (2010). ArticleCAS Google Scholar
Hall, L. L., Smith, K. P., Byron, M. & Lawrence, J. B. Molecular anatomy of a speckle. Anat. Rec. A Discov. Mol. Cell. Evol. Biol.288, 664–675 (2006). ArticlePubMedPubMed Central Google Scholar
Girard, C. et al. Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion. Nature Commun.3, 994 (2012). ArticleCAS Google Scholar
Du, H. & Rosbash, M. The U1 snRNP protein U1C recognizes the 5′ splice site in the absence of base pairing. Nature419, 86–90 (2002). ArticleCASPubMed Google Scholar
Wiesner, S., Stier, G., Sattler, M. & Macias, M. J. Solution structure and ligand recognition of the WW domain pair of the yeast splicing factor Prp40. J. Mol. Biol.324, 807–822 (2002). ArticleCASPubMed Google Scholar
Morris, D. P. & Greenleaf, A. L. The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II. J. Biol. Chem.275, 39935–39943 (2000). ArticleCASPubMed Google Scholar
Gornemann, J. et al. Cotranscriptional spliceosome assembly and splicing are independent of the Prp40p WW domain. RNA17, 2119–2129 (2011). ArticlePubMedPubMed CentralCAS Google Scholar
Staknis, D. & Reed, R. SR proteins promote the first specific recognition of Pre-mRNA and are present together with the U1 small nuclear ribonucleoprotein particle in a general splicing enhancer complex. Mol. Cell. Biol.14, 7670–7682 (1994). ArticleCASPubMedPubMed Central Google Scholar
Cho, S. et al. Interaction between the RNA binding domains of Ser-Arg splicing factor 1 and U1–70K snRNP protein determines early spliceosome assembly. Proc. Natl Acad. Sci. USA108, 8233–8238 (2011). ArticleCASPubMedPubMed Central Google Scholar
Pabis, M. et al. The nuclear cap-binding complex interacts with the U4/U6. U5 tri-snRNP and promotes spliceosome assembly in mammalian cells. RNA19, 1054–1063 (2013). ArticleCASPubMedPubMed Central Google Scholar
Fox-Walsh, K. L. et al. The architecture of pre-mRNAs affects mechanisms of splice-site pairing. Proc. Natl Acad. Sci. USA102, 16176–16181 (2005). ArticleCASPubMedPubMed Central Google Scholar
Xiao, X., Wang, Z., Jang, M. & Burge, C. B. Coevolutionary networks of splicing _cis_-regulatory elements. Proc. Natl Acad. Sci. USA104, 18583–18588 (2007). ArticleCASPubMedPubMed Central Google Scholar
De Conti, L., Baralle, M. & Buratti, E. Exon and intron definition in pre-mRNA splicing. Wiley Interdiscip. Rev. RNA4, 49–60 (2013). ArticleCASPubMed Google Scholar
Bonnal, S. et al. RBM5/Luca-15/H37 regulates Fas alternative splice site pairing after exon definition. Mol. Cell32, 81–95 (2008). ArticleCASPubMed Google Scholar
Sharma, S., Kohlstaedt, L. A., Damianov, A., Rio, D. C. & Black, D. L. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nature Struct. Mol. Biol.15, 183–191 (2008). Demonstrates that an early step in spliceosome assembly (transition from exon definition to intron definition complex) is a key stage for splicing regulation. ArticleCAS Google Scholar
Sun, J. S. & Manley, J. L. A novel U2–U6 snRNA structure is necessary for mammalian mRNA splicing. Genes Dev.9, 843–854 (1995). ArticleCASPubMed Google Scholar
Raghunathan, P. L. & Guthrie, C. RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr. Biol.8, 847–855 (1998). ArticleCASPubMed Google Scholar
Ilagan, J. O., Chalkley, R. J., Burlingame, A. L. & Jurica, M. S. Rearrangements within human spliceosomes captured after exon ligation. RNA19, 400–412 (2013) ArticleCASPubMedPubMed Central Google Scholar
Schwer, B. & Gross, C. H. Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA splicing. EMBO J.17, 2086–2094 (1998). ArticleCASPubMedPubMed Central Google Scholar
Fourmann, J. B. et al. Dissection of the factor requirements for spliceosome disassembly and the elucidation of its dissociation products using a purified splicing system. Genes Dev.27, 413–428 (2013). ArticleCASPubMedPubMed Central Google Scholar
Abelson, J. et al. Conformational dynamics of single pre-mRNA molecules during in vitro splicing. Nature Struct. Mol. Biol.17, 504–512 (2010). ArticleCAS Google Scholar
Tseng, C. K. & Cheng, S. C. Both catalytic steps of nuclear pre-mRNA splicing are reversible. Science320, 1782–1784 (2008). ArticleCASPubMed Google Scholar
Malca, H., Shomron, N. & Ast, G. The U1 snRNP base pairs with the 5′ splice site within a penta–snRNP complex. Mol. Cell. Biol.23, 3442–3455 (2003). ArticleCASPubMedPubMed Central Google Scholar
Stevens, S. W. et al. Composition and functional characterization of the yeast spliceosomal penta–snRNP. Mol. Cell9, 31–44 (2002). ArticleCASPubMed Google Scholar
Gornemann, J., Kotovic, K. M., Hujer, K. & Neugebauer, K. M. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol. Cell19, 53–63 (2005). Development of a novel chromatin immunoprecipitation assay to investigate co-transcriptional spliceosome assembly, demonstrating a role for the CBC in recruitment of snRNPs to nascent pre-mRNA transcripts. ArticlePubMedCAS Google Scholar
Behzadnia, N., Hartmuth, K., Will, C. L. & Luhrmann, R. Functional spliceosomal A complexes can be assembled in vitro in the absence of a penta–snRNP. RNA12, 1738–1746 (2006). ArticleCASPubMedPubMed Central Google Scholar
Schneider, M. et al. Exon definition complexes contain the tri-snRNP and can be directly converted into B-like precatalytic splicing complexes. Mol. Cell38, 223–235 (2010). Together with reference 116, these studies suggest the existence of alternative spliceosome assembly pathways. ArticleCASPubMed Google Scholar
Madhani, H. D. & Guthrie, C. Dynamic RNA–RNA interactions in the spliceosome. Annu. Rev. Genet.28, 1–26 (1994). ArticleCASPubMed Google Scholar
Valadkhan, S., Mohammadi, A., Wachtel, C. & Manley, J. L. Protein-free spliceosomal snRNAs catalyze a reaction that resembles the first step of splicing. RNA13, 2300–2311 (2007). ArticleCASPubMedPubMed Central Google Scholar
Valadkhan, S., Mohammadi, A., Jaladat, Y. & Geisler, S. Protein-free small nuclear RNAs catalyze a two-step splicing reaction. Proc. Natl Acad. Sci. USA106, 11901–11906 (2009). Together with reference 122, demonstrates that protein-free U6/U2 snRNA constructs can recognize 5′ splice site and branch point sequence to carry out the first and second steps of splicing. ArticleCASPubMedPubMed Central Google Scholar
Cordin, O., Hahn, D. & Beggs, J. D. Structure, function and regulation of spliceosomal RNA helicases. Curr. Opin. Cell Biol.24, 431–438 (2012). ArticleCASPubMed Google Scholar
Small, E. C., Leggett, S. R., Winans, A. A. & Staley, J. P. The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase. Mol. Cell23, 389–399 (2006). ArticleCASPubMedPubMed Central Google Scholar
Galej, W. P., Oubridge, C., Newman, A. J. & Nagai, K. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature493, 638–643 (2013). ArticleCASPubMedPubMed Central Google Scholar
Schellenberg, M. J. et al. A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation. Nature Struct. Mol. Biol.20, 728–734 (2013). ArticleCAS Google Scholar
Mozaffari-Jovin, S. et al. Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science341, 80–84 (2013). ArticleCASPubMed Google Scholar
Ohrt, T. et al. Molecular dissection of step 2 catalysis of yeast pre-mRNA splicing investigated in a purified system. RNA19, 902–915 (2013). ArticleCASPubMedPubMed Central Google Scholar
Matlin, A. J., Clark, F. & Smith, C. W. Understanding alternative splicing: towards a cellular code. Nature Rev. Mol. Cell Biol.6, 386–398 (2005). ArticleCAS Google Scholar
Wang, Z. & Burge, C. B. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA14, 802–813 (2008). ArticleCASPubMedPubMed Central Google Scholar
Bessonov, S., Anokhina, M., Will, C. L., Urlaub, H. & Luhrmann, R. Isolation of an active step I spliceosome and composition of its RNP core. Nature452, 846–850 (2008). ArticleCASPubMed Google Scholar
Zhou, Z., Licklider, L. J., Gygi, S. P. & Reed, R. Comprehensive proteomic analysis of the human spliceosome. Nature419, 182–185 (2002). Identifies more than 100 proteins in the active spliceosome, many more than the known protein components of snRNPs. ArticleCASPubMed Google Scholar
Hegele, A. et al. Dynamic protein–protein interaction wiring of the human spliceosome. Mol. Cell45, 567–580 (2012). ArticleCASPubMed Google Scholar
Izquierdo, J. M. et al. Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Mol. Cell19, 475–484 (2005). ArticleCASPubMed Google Scholar
Sharma, S., Maris, C., Allain, F. H. & Black, D. L. U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression. Mol. Cell41, 579–588 (2011). ArticleCASPubMedPubMed Central Google Scholar
Chiou, N. T., Shankarling, G. & Lynch, K. W. HnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Mol. Cell49, 972–982 (2013). ArticleCASPubMedPubMed Central Google Scholar
House, A. E. & Lynch, K. W. An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition. Nature Struct. Mol. Biol.13, 937–944 (2006). ArticleCAS Google Scholar
McCullough, A. J. & Berget, S. M. G triplets located throughout a class of small vertebrate introns enforce intron borders and regulate splice site selection. Mol. Cell. Biol.17, 4562–4571 (1997). ArticleCASPubMedPubMed Central Google Scholar
Chou, M. Y., Rooke, N., Turck, C. W. & Black, D. L. hnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells. Mol. Cell. Biol.19, 69–77 (1999). ArticleCASPubMedPubMed Central Google Scholar
Chen, C. D., Kobayashi, R. & Helfman, D. M. Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat β-tropomyosin gene. Genes Dev.13, 593–606 (1999). ArticleCASPubMedPubMed Central Google Scholar
Caputi, M. & Zahler, A. M. Determination of the RNA binding specificity of the heterogeneous nuclear ribonucleoprotein (hnRNP) H/H′/F/2H9 family. J. Biol. Chem.276, 43850–43859 (2001). ArticleCASPubMed Google Scholar
Ule, J. et al. An RNA map predicting Nova-dependent splicing regulation. Nature444, 580–586 (2006). ArticleCASPubMed Google Scholar
Wang, Y. et al. A complex network of factors with overlapping affinities represses splicing through intronic elements. Nature Struct. Mol. Biol.20, 36–45 (2013). Suggests that interactions between variouscis-acting elements andtrans-acting factors form a complex network that controls context-dependent splicing. ArticleCAS Google Scholar
Borah, S., Wong, A. C. & Steitz, J. A. Drosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron. Proc. Natl Acad. Sci. USA106, 2577–2582 (2009). ArticleCASPubMedPubMed Central Google Scholar
Wang, Z. et al. Systematic identification and analysis of exonic splicing silencers. Cell119, 831–845 (2004). ArticleCASPubMed Google Scholar
Yu, Y. et al. Dynamic regulation of alternative splicing by silencers that modulate 5′ splice site competition. Cell135, 1224–1236 (2008). ArticleCASPubMedPubMed Central Google Scholar
Donahue, C. P., Muratore, C., Wu, J. Y., Kosik, K. S. & Wolfe, M. S. Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing. J. Biol. Chem.281, 23302–23306 (2006). ArticleCASPubMed Google Scholar
Graveley, B. R. Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures. Cell123, 65–73 (2005). A great example of how RNA structures can have a leading role in controlling a complicated regimen of mutally exclusive splicing. ArticleCASPubMedPubMed Central Google Scholar
Yang, Y. et al. RNA secondary structure in mutually exclusive splicing. Nature Struct. Mol. Biol.18, 159–168 (2011). ArticleCAS Google Scholar
Wang, X. et al. An RNA architectural locus control region involved in Dscam mutually exclusive splicing. Nature Commun.3, 1255 (2012). ArticleCAS Google Scholar
Bleichert, F. & Baserga, S. J. The long unwinding road of RNA helicases. Mol. Cell27, 339–352 (2007). ArticleCASPubMed Google Scholar
Honig, A., Auboeuf, D., Parker, M. M., O'Malley, B. W. & Berget, S. M. Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72. Mol. Cell. Biol.22, 5698–5707 (2002). ArticleCASPubMedPubMed Central Google Scholar
Lee, C. G. RH70, a bidirectional RNA helicase, co-purifies with U1snRNP. J. Biol. Chem.277, 39679–39683 (2002). ArticleCASPubMed Google Scholar
Khodor, Y. L. et al. Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila. Genes Dev.25, 2502–2512 (2011). ArticleCASPubMedPubMed Central Google Scholar
Ip, J. Y. et al. Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation. Genome Res.21, 390–401 (2011). ArticleCASPubMedPubMed Central Google Scholar
Roberts, G. C., Gooding, C., Mak, H. Y., Proudfoot, N. J. & Smith, C. W. Co-transcriptional commitment to alternative splice site selection. Nucleic Acids Res.26, 5568–5572 (1998). ArticleCASPubMedPubMed Central Google Scholar
Kornblihtt, A. R. et al. Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nature Rev. Mol. Cell Biol.14, 153–165 (2013). ArticleCAS Google Scholar
Wang, Y., Ma, M., Xiao, X. & Wang, Z. Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules. Nature Struct. Mol. Biol.19, 1044–1052 (2012). ArticleCAS Google Scholar
Spellman, R., Llorian, M. & Smith, C. W. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol. Cell27, 420–434 (2007). ArticleCASPubMedPubMed Central Google Scholar
Boutz, P. L. et al. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev.21, 1636–1652 (2007). ArticleCASPubMedPubMed Central Google Scholar
Tanackovic, G. et al. PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa. Hum. Mol. Genet.20, 2116–2130 (2011). ArticleCASPubMedPubMed Central Google Scholar
Utz, V. M., Beight, C. D., Marino, M. J., Hagstrom, S. A. & Traboulsi, E. I. Autosomal dominant retinitis pigmentosa secondary to pre-mRNA splicing-factor gene PRPF31 (RP11): review of disease mechanism and report of a family with a novel 3-base pair insertion. Ophthalm. Genet.34, 183–188 (2013). ArticleCAS Google Scholar
Pena, V., Liu, S., Bujnicki, J. M., Luhrmann, R. & Wahl, M. C. Structure of a multipartite protein–protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol. Cell25, 615–624 (2007). ArticleCASPubMed Google Scholar
He, H. et al. Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. Science332, 238–240 (2011). ArticleCASPubMedPubMed Central Google Scholar
Lorson, C. L., Hahnen, E., Androphy, E. J. & Wirth, B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl Acad. Sci. USA96, 6307–6311 (1999). ArticleCASPubMedPubMed Central Google Scholar
Schrank, B. et al. Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc. Natl Acad. Sci. USA94, 9920–9925 (1997). ArticleCASPubMedPubMed Central Google Scholar
Gabanella, F. et al. Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS ONE2, e921 (2007). ArticlePubMedPubMed CentralCAS Google Scholar
Praveen, K., Wen, Y. & Matera, A. G. A. Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects. Cell Rep.1, 624–631 (2012). ArticleCASPubMedPubMed Central Google Scholar
Garcia, E. L., Lu, Z., Meers, M. P., Praveen, K. & Matera, A. G. Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes. RNA19, 1510–1516 (2013). ArticleCASPubMedPubMed Central Google Scholar
Baumer, D. et al. Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet.5, e1000773 (2009). Together with references 182 and 183, these studies show that SMA phenotypes can be uncoupled from global splicing deficits. Using a missense allele that is active in Sm core assembly, reference 184 reveals a separation of SMN functions. ArticlePubMedPubMed CentralCAS Google Scholar
Cazzola, M., Rossi, M. & Malcovati, L. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood121, 260–269 (2013). ArticleCASPubMedPubMed Central Google Scholar
Yoshida, K. et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature478, 64–69 (2011). ArticleCASPubMed Google Scholar
Chesnais, V. et al. Spliceosome mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia. Oncotarget3, 1284–1293 (2012). ArticlePubMedPubMed Central Google Scholar
Dhir, A., Buratti, E., van Santen, M. A., Luhrmann, R. & Baralle, F. E. The intronic splicing code: multiple factors involved in ATM pseudoexon definition. EMBO J.29, 749–760 (2010). ArticleCASPubMedPubMed Central Google Scholar
Lewandowska, M. A., Stuani, C., Parvizpur, A., Baralle, F. E. & Pagani, F. Functional studies on the ATM intronic splicing processing element. Nucleic Acids Res.33, 4007–4015 (2005). ArticleCASPubMedPubMed Central Google Scholar
Pagani, F. et al. A new type of mutation causes a splicing defect in ATM. Nature Genet.30, 426–429 (2002). ArticleCASPubMed Google Scholar
Gunderson, S. I., Polycarpou-Schwarz, M. & Mattaj, I. W. U1 snRNP inhibits pre-mRNA polyadenylation through a direct interaction between U1 70K and poly(A) polymerase. Mol. Cell1, 255–264 (1998). ArticleCASPubMed Google Scholar
Langemeier, J., Radtke, M. & Bohne, J. U1 snRNP-mediated poly(A) site suppression: beneficial and deleterious for mRNA fate. RNA Biol.10, 180–184 (2013). ArticleCASPubMedPubMed Central Google Scholar
Almada, A. E., Wu, X., Kriz, A. J., Burge, C. B. & Sharp, P. A. Promoter directionality is controlled by U1 snRNP and polyadenylation signals. Nature499, 360–363 (2013). ArticleCASPubMedPubMed Central Google Scholar
Berg, M. G. et al. U1 snRNP determines mRNA length and regulates isoform expression. Cell150, 53–64 (2012). Together with reference 193, these genome-wide analyses illustrate a pervasive, non-splicing role for U1 snRNP in selection of the site of pre-mRNA 3′-end cleavage and polyadenylation. ArticleCASPubMedPubMed Central Google Scholar
Peterson, M. L., Bingham, G. L. & Cowan, C. Multiple features contribute to the use of the immunoglobulin M secretion-specific poly(A) signal but are not required for developmental regulation. Mol. Cell. Biol.26, 6762–6771 (2006). ArticleCASPubMedPubMed Central Google Scholar
Hall-Pogar, T., Liang, S., Hague, L. K. & Lutz, C. S. Specific _trans_-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3′-UTR. RNA13, 1103–1115 (2007). ArticleCASPubMedPubMed Central Google Scholar
Luo, W. et al. 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 Genet.9, e1003613 (2013). ArticleCASPubMedPubMed Central Google Scholar
Michaeli, S. Trans-splicing in trypanosomes: machinery and its impact on the parasite transcriptome. Future Microbiol.6, 459–474 (2011). ArticleCASPubMed Google Scholar
Bruzik, J. P. & Maniatis, T. Spliced leader RNAs from lower eukaryotes are _trans_-spliced in mammalian cells. Nature360, 692–695 (1992). ArticleCASPubMed Google Scholar
Fabrizio, P. et al. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol. Cell36, 593–608 (2009). ArticleCASPubMed Google Scholar