Genomes and Genes
u2 small nuclear ribonucleoprotein
Summary: A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U2 snRNP along with other small nuclear ribonucleoproteins (U1, U4-U6, and U5) assemble into SPLICEOSOMES that remove introns from pre-mRNA by splicing. The U2 snRNA forms base pairs with conserved sequence motifs at the branch point, which associates with a heat- and RNAase-sensitive factor in an early step of splicing.
- Pauling M, McPheeters D, Ares M. Functional Cus1p is found with Hsh155p in a multiprotein splicing factor associated with U2 snRNA. Mol Cell Biol. 2000;20:2176-85 pubmed..The Cus1p complex shares functional as well as structural similarities with human SF3b. ..
- Cline T, Rudner D, Barbash D, Bell M, Vutien R. Functioning of the Drosophila integral U1/U2 protein Snf independent of U1 and U2 small nuclear ribonucleoprotein particles is revealed by snf(+) gene dose effects. Proc Natl Acad Sci U S A. 1999;96:14451-8 pubmed..is the Drosophila homolog of mammalian U1A and U2B" and is an integral component of U1 and U2 small nuclear ribonucleoprotein particles (snRNPs)...
- Golas M, Sander B, Will C, Luhrmann R, Stark H. Molecular architecture of the multiprotein splicing factor SF3b. Science. 2003;300:980-4 pubmed..As an integral component of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP, SF3b is involved in the recognition of the pre-messenger RNA's ..
- Banerjee H, Rahn A, Davis W, Singh R. Sex lethal and U2 small nuclear ribonucleoprotein auxiliary factor (U2AF65) recognize polypyrimidine tracts using multiple modes of binding. RNA. 2003;9:88-99 pubmed..The results indicate that multiple modes of binding result in an ensemble of RNA-protein complexes, which could allow tuning of the binding affinity without changing sequence specificity. ..
- Wiest D, O Day C, Abelson J. In vitro studies of the Prp9.Prp11.Prp21 complex indicate a pathway for U2 small nuclear ribonucleoprotein activation. J Biol Chem. 1996;271:33268-76 pubmed..We present a model, based on the data presented here and in the accompanying paper, for a combined role of Prp9, Prp11, Prp21, and Prp5 in activating the U2 snRNP for assembly into the pre-spliceosome. ..
- Gozani O, Feld R, Reed R. Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A. Genes Dev. 1996;10:233-43 pubmed..These data indicate that sequence-independent binding of the highly conserved SF3a/SF3b subunits upstream of the branch site is essential for anchoring U2 snRNP to pre-mRNA. ..
- Wells S, Neville M, Haynes M, Wang J, Igel H, Ares M. CUS1, a suppressor of cold-sensitive U2 snRNA mutations, is a novel yeast splicing factor homologous to human SAP 145. Genes Dev. 1996;10:220-32 pubmedThe function of U2 snRNA in splicing is mediated by the proteins of the U2 small nuclear ribonucleoprotein. To identify proteins that influence the function of U2 snRNA we carried out a screen for mutations in Saccharomyces cerevisiae ..
- Boudrez A, Beullens M, Waelkens E, Stalmans W, Bollen M. Phosphorylation-dependent interaction between the splicing factors SAP155 and NIPP1. J Biol Chem. 2002;277:31834-41 pubmed..vivo with a TP dipeptide-rich fragment of the splicing factor SAP155/SF3b(155), a component of the U2 small nuclear ribonucleoprotein particle...
- Gozani O, Potashkin J, Reed R. A potential role for U2AF-SAP 155 interactions in recruiting U2 snRNP to the branch site. Mol Cell Biol. 1998;18:4752-60 pubmed..Together, our data are consistent with a model in which U2AF binds to the pyrimidine tract in the E complex and then interacts with SAP 155 to recruit U2 snRNP to the BPS. ..
- Kuwasako K, Dohmae N, Inoue M, Shirouzu M, Taguchi S, Güntert P, et al. Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analyses. Proteins. 2008;71:1617-36 pubmedThe spliceosomal protein p14, a component of the SF3b complex in the U2 small nuclear ribonucleoprotein (snRNP), is essential for the U2 snRNP to recognize the branch site adenosine...
- Abu Dayyeh B, Quan T, Castro M, Ruby S. Probing interactions between the U2 small nuclear ribonucleoprotein and the DEAD-box protein, Prp5. J Biol Chem. 2002;277:20221-33 pubmedPre-mRNA binding to the yeast U2 small nuclear ribonucleoprotein (snRNP) during prespliceosome formation requires ATP hydrolysis, the highly conserved UACUAAC box of the branch point region of the pre-mRNA, and several factors...
- Tang J, Abovich N, Rosbash M. Identification and characterization of a yeast gene encoding the U2 small nuclear ribonucleoprotein particle B" protein. Mol Cell Biol. 1996;16:2787-95 pubmed..Surprisingly, the YU2B" protein lacks a C-terminal RNA binding domain, which is conserved in all other family members. Possible functional and evolutionary relationships among these proteins are discussed. ..
- Golas M, Sander B, Will C, Luhrmann R, Stark H. Major conformational change in the complex SF3b upon integration into the spliceosomal U11/U12 di-snRNP as revealed by electron cryomicroscopy. Mol Cell. 2005;17:869-83 pubmed..The manner in which SF3b is integrated in the U11/U12 di-snRNP has important implications for branch site recognition. Furthermore, a putative model of the pre-mRNA binding to the U11/U12 di-snRNP is proposed. ..
- Dziembowski A, Ventura A, Rutz B, Caspary F, Faux C, Halgand F, et al. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 2004;23:4847-56 pubmed..The corresponding complex was named pre-mRNA REtention and Splicing (RES). The presence of RES subunit homologues in numerous eukaryotes suggests that its function is evolutionarily conserved. ..
- Feng Y, Chen M, Manley J. Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. Nat Struct Mol Biol. 2008;15:1040-8 pubmed publisher..Together, our data demonstrate that SRp38, in addition to its role as a splicing repressor, can function as an unusual sequence-specific splicing activator. ..
- Lin K, Lu R, Tarn W. The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo. Mol Cell Biol. 2004;24:9176-85 pubmed..The WW domains associate preferentially with the U2 small nuclear ribonucleoprotein and with splicing factors SF1, U2AF, and components of the SF3 complex...
- Tanuma N, Kim S, Beullens M, Tsubaki Y, Mitsuhashi S, Nomura M, et al. Nuclear inhibitor of protein phosphatase-1 (NIPP1) directs protein phosphatase-1 (PP1) to dephosphorylate the U2 small nuclear ribonucleoprotein particle (snRNP) component, spliceosome-associated protein 155 (Sap155). J Biol Chem. 2008;283:35805-14 pubmed publisher..nucleus, recruits PP1 to Sap155 (spliceosome-associated protein 155), an essential component of U2 small nuclear ribonucleoprotein particles, and promotes Sap155 dephosphorylation...
- Jurica M, Sousa D, Moore M, Grigorieff N. Three-dimensional structure of C complex spliceosomes by electron microscopy. Nat Struct Mol Biol. 2004;11:265-9 pubmed..The structure reveals a particle of dimensions 27 x 22 x 24 nm with a relatively open arrangement of three primary domains. ..
- Dybkov O, Will C, Deckert J, Behzadnia N, Hartmuth K, Luhrmann R. U2 snRNA-protein contacts in purified human 17S U2 snRNPs and in spliceosomal A and B complexes. Mol Cell Biol. 2006;26:2803-16 pubmed..These studies provide important insights into the molecular architecture of 17S U2 snRNPs and reveal U2 snRNP remodeling events during spliceosome assembly. ..
- Flickinger T, Salz H. The Drosophila sex determination gene snf encodes a nuclear protein with sequence and functional similarity to the mammalian U1A snRNP protein. Genes Dev. 1994;8:914-25 pubmed..These studies provide the first demonstration, in a multicellular organism, that mutations in a U1 snRNP protein alter splicing in vivo. ..
- Corsini L, Bonnal S, Bonna S, Basquin J, Hothorn M, Scheffzek K, et al. U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat Struct Mol Biol. 2007;14:620-9 pubmed..Our data suggest that networks of UHM-ULM interactions are involved in regulating alternative splicing. ..
- Izquierdo J. Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definition. J Biol Chem. 2008;283:19077-84 pubmed publisher..HuR inhibits the association of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 kDa (U2AF65) with the upstream 3' splice site, without decreasing ..
- Preusser C, Palfi Z, Bindereif A. Special Sm core complex functions in assembly of the U2 small nuclear ribonucleoprotein of Trypanosoma brucei. Eukaryot Cell. 2009;8:1228-34 pubmed publisher..Together they form a high-affinity, U2-specific binding complex. This trypanosome-specific assembly differs from the mammalian system and provides a functional role for the Sm core variation found in the trypanosomal U2 snRNP. ..
- Wells S, Ares M. Interactions between highly conserved U2 small nuclear RNA structures and Prp5p, Prp9p, Prp11p, and Prp21p proteins are required to ensure integrity of the U2 small nuclear ribonucleoprotein in Saccharomyces cerevisiae. Mol Cell Biol. 1994;14:6337-49 pubmedBinding of U2 small nuclear ribonucleoprotein (snRNP) to the pre-mRNA is an early and important step in spliceosome assembly...
- Martinez E, Palhan V, Tjernberg A, Lymar E, Gamper A, Kundu T, et al. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. Mol Cell Biol. 2001;21:6782-95 pubmed
- Wang C, Chua K, Seghezzi W, Lees E, Gozani O, Reed R. Phosphorylation of spliceosomal protein SAP 155 coupled with splicing catalysis. Genes Dev. 1998;12:1409-14 pubmed..Significantly, SAP 155 is phosphorylated concomitant with or just after catalytic step one, making this the first example of a protein modification tightly regulated with splicing catalysis. ..
- Polycarpou Schwarz M, Gunderson S, Kandels Lewis S, Seraphin B, Mattaj I. Drosophila SNF/D25 combines the functions of the two snRNP proteins U1A and U2B' that are encoded separately in human, potato, and yeast. RNA. 1996;2:11-23 pubmed..Thus, its RNA-binding properties are the sum of those exhibited by human or potato U1A and U2B' proteins. Implications for the role of SNF/D25 in alternative splicing, and for the evolution of the U1A/U2B' protein family, are discussed. ..
- Matera A, Shpargel K. Pumping RNA: nuclear bodybuilding along the RNP pipeline. Curr Opin Cell Biol. 2006;18:317-24 pubmed
- Wang Q, Rymond B. Rds3p is required for stable U2 snRNP recruitment to the splicing apparatus. Mol Cell Biol. 2003;23:7339-49 pubmed..Together these data establish Rds3p as an essential component of the U2 snRNP SF3b complex and suggest a new link between the nuclear processes of pre-mRNA splicing and RNA export. ..
- Seghezzi W, Chua K, Shanahan F, Gozani O, Reed R, Lees E. Cyclin E associates with components of the pre-mRNA splicing machinery in mammalian cells. Mol Cell Biol. 1998;18:4526-36 pubmed..These findings provide evidence that pre-mRNA splicing may be linked to the cell cycle machinery in mammalian cells. ..
- Will C, Schneider C, MacMillan A, Katopodis N, Neubauer G, Wilm M, et al. A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site. EMBO J. 2001;20:4536-46 pubmed..Immuno precipitations indicated that p14 is present in U12-type spliceosomes, consistent with the idea that branch point selection is similar in the major and minor spliceosomes. ..
- Domon C, Lorković Z, Valcarcel J, Filipowicz W. Multiple forms of the U2 small nuclear ribonucleoprotein auxiliary factor U2AF subunits expressed in higher plants. J Biol Chem. 1998;273:34603-10 pubmed..The existence of multiple isoforms of U2AF may be quite general in plants because two genes expressing U2AF65 have been identified in Arabidopsis, and different isoforms of the U2AF small subunit are expressed in rice. ..
- Suk K, Kim S, Kim Y, Oh S, Lee M, Kim K, et al. Identification of a novel human member of the DEAD box protein family. Biochim Biophys Acta. 2000;1501:63-9 pubmed..In vivo or in vitro functions of RHELP as a putative RNA helicase and its potential role as a diabetic autoantigen need to be further investigated. ..
- Will C, 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 pubmed..Taken together, these studies provide new insight into the composition of the 17S U2 snRNP and the potential function of several of its proteins. ..
- Gottschalk A, Bartels C, Neubauer G, Luhrmann R, Fabrizio P. A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step of splicing and for progression of spliceosome assembly. Mol Cell Biol. 2001;21:3037-46 pubmed..We demonstrate that Snu17p binds specifically to the U2 small nuclear ribonucleoprotein (snRNP) and that it is part of the spliceosome, since the pre-mRNA and the lariat-exon 2 are ..
- Sharma S, Kohlstaedt L, Damianov A, Rio D, Black D. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nat Struct Mol Biol. 2008;15:183-91 pubmed publisher..Trans-splicing experiments indicated that, even when the U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) are properly bound to the upstream and downstream exons, the presence of PTB ..
- Kotake Y, Sagane K, Owa T, Mimori Kiyosue Y, Shimizu H, Uesugi M, et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol. 2007;3:570-5 pubmed..Our results demonstrate that the SF3b complex is a pharmacologically relevant protein target of pladienolide and suggest that this splicing factor is a potential antitumor drug target. ..
- Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, et al. Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nat Chem Biol. 2007;3:576-83 pubmed..inhibit in vitro splicing and promote pre-mRNA accumulation by binding to SF3b, a subcomplex of the U2 small nuclear ribonucleoprotein in the spliceosome...
- Boukis L, Liu N, Furuyama S, Bruzik J. Ser/Arg-rich protein-mediated communication between U1 and U2 small nuclear ribonucleoprotein particles. J Biol Chem. 2004;279:29647-53 pubmed..These results demonstrate that SR proteins are required for communication between U1 and U2 snRNPs whether this interaction is across introns or exons. ..
- Ségault V, Will C, Sproat B, Luhrmann R. In vitro reconstitution of mammalian U2 and U5 snRNPs active in splicing: Sm proteins are functionally interchangeable and are essential for the formation of functional U2 and U5 snRNPs. EMBO J. 1995;14:4010-21 pubmed..In contrast, splicing could not be restored to U2-depleted extract by the addition of snRNPs reconstituted from synthetic U2 snRNA, suggesting that U2 snRNA base modifications are essential for U2 snRNP function. ..
- Schellenberg M, Edwards R, Ritchie D, Kent O, Golas M, Stark H, et al. Crystal structure of a core spliceosomal protein interface. Proc Natl Acad Sci U S A. 2006;103:1266-71 pubmed..SF3b155 presents a noncanonical surface for RNA recognition at the heart of the mammalian spliceosome. ..
- Eldridge A, Li Y, Sharp P, Blencowe B. The SRm160/300 splicing coactivator is required for exon-enhancer function. Proc Natl Acad Sci U S A. 1999;96:6125-30 pubmed..The association of SRm160/300 and U2 small nuclear ribonucleoprotein particle (snRNP) with this pre-mRNA requires both U1 snRNP and factors bound to the ESE...
- Kuhn A, van Santen M, Schwienhorst A, Urlaub H, Luhrmann R. Stalling of spliceosome assembly at distinct stages by small-molecule inhibitors of protein acetylation and deacetylation. RNA. 2009;15:153-75 pubmed publisher..This suggests that the stalled complexes represent hitherto unobserved intermediates of spliceosome assembly. ..
- Uhlmann Schiffler H, Jalal C, Stahl H. Ddx42p--a human DEAD box protein with RNA chaperone activities. Nucleic Acids Res. 2006;34:10-22 pubmed..The adenosine nucleotide cofactor bound to Ddx42p apparently acts as a switch that controls the two opposing activities: ATP triggers RNA strand separation, whereas ADP triggers annealing of complementary RNA strands. ..
- Plaschka C, Lin P, Nagai K. Structure of a pre-catalytic spliceosome. Nature. 2017;546:617-621 pubmed publisher..The mobile U2 small nuclear ribonucleoprotein particle (snRNP) associates with U4/U6...
- Cretu C, Schmitzová J, Ponce Salvatierra A, Dybkov O, De Laurentiis E, Sharma K, et al. Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations. Mol Cell. 2016;64:307-319 pubmed publisherSF3b is a heptameric protein complex of the U2 small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing...
- Freund M, Asang C, Kammler S, Konermann C, Krummheuer J, Hipp M, et al. A novel approach to describe a U1 snRNA binding site. Nucleic Acids Res. 2003;31:6963-75 pubmed..Mutating GAR nucleotide repeats within this site decreased the SD4-dependent Rev-mediated env expression, which could be balanced simply by artificially increasing the complementarity of SD4. ..
- Cote J, Dupuis S, Jiang Z, Wu J. Caspase-2 pre-mRNA alternative splicing: Identification of an intronic element containing a decoy 3' acceptor site. Proc Natl Acad Sci U S A. 2001;98:938-43 pubmed..These results reveal a mechanism of action for a negative intronic regulatory element and uncover a role for U2 snRNP in the regulation of alternative splicing. ..
- Horie A, Isono K, Koseki H. Generation of a monoclonal antibody against the mouse Sf3b1 (SAP155) gene product for U2 snRNP component of spliceosome. Hybrid Hybridomics. 2003;22:117-9 pubmed..In this study, we report the generation of a monoclonal antibody (MAb) against murine Sf3b1 protein. This MAb recognizes endogenous Sf3b1 gene product by Western blotting, but less efficiently by immunoprecipitation. ..
- Luo M, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, et al. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001;413:644-7 pubmed..These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP. ..
- Rymond B. Targeting the spliceosome. Nat Chem Biol. 2007;3:533-5 pubmed
- Marzluff W. U2 snRNP: not just for poly(A) mRNAs. Mol Cell. 2007;28:353-4 pubmed..Friend et al. (2007) now report that the U2 snRNP, required for pre-mRNA splicing, is also required for histone mRNA 3' end formation. ..
- Luo H, Moreau G, Levin N, Moore M. The human Prp8 protein is a component of both U2- and U12-dependent spliceosomes. RNA. 1999;5:893-908 pubmed..These spliceosomes, which excise different classes of introns, contain distinct sets of snRNAs overlapping only with U5 snRNA. Other than the core Sm proteins, hPrp8p is the first splicing factor shown to be common to both spliceosomes. ..
- Rohde J, Campbell S, Zurita Martinez S, Cutler N, Ashe M, Cardenas M. TOR controls transcriptional and translational programs via Sap-Sit4 protein phosphatase signaling effectors. Mol Cell Biol. 2004;24:8332-41 pubmed..We conclude that Tor signals via Sap-Sit4 complexes to control both transcriptional and translational programs that couple cell growth to amino acid availability. ..
- Patel S, Novikova N, Bellini M. Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts. J Cell Biol. 2007;178:937-49 pubmed..Collectively, these data indicate that the recruitment of snRNPs to nascent transcripts and the assembly of the spliceosome are uncoupled events. ..
- McPheeters D, Muhlenkamp P. Spatial organization of protein-RNA interactions in the branch site-3' splice site region during pre-mRNA splicing in yeast. Mol Cell Biol. 2003;23:4174-86 pubmed..Taken together, these data provide a detailed portrayal of the dynamic associations of proteins with the branch site-3' splice site region during spliceosome assembly and catalysis. ..
- Blencowe B, Carmo Fonseca M, Behrens S, Luhrmann R, Lamond A. Interaction of the human autoantigen p150 with splicing snRNPs. J Cell Sci. 1993;105 ( Pt 3):685-97 pubmed..Addition of the purified U4/U6.U5 tri-snRNP restores splicing activity to inactivated HeLa nuclear extracts in which splicing had been inhibited by specific depletion of either the U4/U6 or U5 snRNPs. ..
- Corsini L, Hothorn M, Stier G, Rybin V, Scheffzek K, Gibson T, et al. Dimerization and protein binding specificity of the U2AF homology motif of the splicing factor Puf60. J Biol Chem. 2009;284:630-9 pubmed publisher..Our data suggest that the functional cooperativity between U2AF65 and Puf60 may involve simultaneous interactions of the two proteins with SF3b155. ..
- Massenet S, Motorin Y, Lafontaine D, Hurt E, Grosjean H, Branlant C. Pseudouridine mapping in the Saccharomyces cerevisiae spliceosomal U small nuclear RNAs (snRNAs) reveals that pseudouridine synthase pus1p exhibits a dual substrate specificity for U2 snRNA and tRNA. Mol Cell Biol. 1999;19:2142-54 pubmed..As depletion of rRNA-pseudouridine synthase Cbf5p had no effect on UsnRNA Psi content, formation of Psi residues in S. cerevisiae UsnRNAs is not dependent on the Cbf5p-snoRNA guided mechanism. ..
- Chaouki A, Salz H. Drosophila SPF45: a bifunctional protein with roles in both splicing and DNA repair. PLoS Genet. 2006;2:e178 pubmed
- 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 pubmed..These studies provide another example of coilin's role in the functional organization of the nucleus. ..
- Damgaard C, Tange T, Kjems J. hnRNP A1 controls HIV-1 mRNA splicing through cooperative binding to intron and exon splicing silencers in the context of a conserved secondary structure. RNA. 2002;8:1401-15 pubmed