| Structural highlights
Function
[RSMB_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [NCBP2_YEAST] Component of the CBC complex, which binds co-transcriptionally to the cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [SNU56_YEAST] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway. [RU1C_YEAST] Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. YHC1/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.[11] [12] [13] [RUXG_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [RU17_YEAST] Involved in nuclear mRNA splicing. [SMD2_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [RUXF_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [NAM8_YEAST] Acts as a suppressor of mitochondrial splicing deficiencies when overexpressed. Could be a non-essential component of the mitochondrial splicing machinery. [RU1A_YEAST] Involved in nuclear mRNA splicing. The principal role of the U1A is to help fold or maintain U1 RNA in an active configuration. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP.[14] [15] [LUC7_YEAST] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway.[16] [17] [SMD1_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.[18] [19] [SMD3_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.[20] [21] [RUXE_YEAST] Involved in pre-mRNA splicing. Binds and is required for the stability of snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Involved in cap modification.[22] [NCBP1_YEAST] Component of the CBC complex, which binds co-transcriptionally to the 5'-cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs. The CBC complex is required for efficient pre-mRNA splicing through efficient commitment complex and spliceosome formation. Together with NPL3, the CBC complex is required for export of mRNAs out of the nucleus. The CBC complex is also involved in nuclear mRNA degradation, probably by directing the mRNAs to the sites of degradation. Affects replication of the positive-strand RNA virus BMV.[23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [SNU71_YEAST] Component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway.[36] [PRP42_YEAST] Essential component of the U1 snRNP particle, which recognizes and binds the 5'-splice site of pre-mRNA. Together with other non-snRNP factors, U1 snRNP forms the spliceosomal commitment complex, that targets pre-mRNA to the splicing pathway. U1 snRNP is cotranscriptionally recruited to intron-containing genes. Required for U1 snRNP biogenesis.[37] [38] [PRP40_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U1. Two commitment complexes, CC1 and CC2, have been defined in yeast. CC1 is a basal complex dependent only on the 5' splice site. CC2 is a complex of lower mobility and is dependent on a branchpoint as well as a 5' splice site region. This protein is involved in CC2 formation where it binds to the branchpoint binding protein MSL5, bridging the U1 snRNP-associated 5' splice site and the MSL5-associated branch point 3' intron splice site.[39] [40] [41] [PRP39_YEAST] Function prior to stable branch point recognition by the U1 snRNP particle to facilitate or stabilize the U1 snRNP/5'-splice site interaction. Has a direct role in the assembly or function of a catalytically active spliceosome.
Publication Abstract from PubMed
The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.
A unified mechanism for intron and exon definition and back-splicing.,Li X, Liu S, Zhang L, Issaian A, Hill RC, Espinosa S, Shi S, Cui Y, Kappel K, Das R, Hansen KC, Zhou ZH, Zhao R Nature. 2019 Sep;573(7774):375-380. doi: 10.1038/s41586-019-1523-6. Epub 2019 Sep, 4. PMID:31485080[42]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fortes P, Kufel J, Fornerod M, Polycarpou-Schwarz M, Lafontaine D, Tollervey D, Mattaj IW. Genetic and physical interactions involving the yeast nuclear cap-binding complex. Mol Cell Biol. 1999 Oct;19(10):6543-53. PMID:10490594
- ↑ Shen EC, Stage-Zimmermann T, Chui P, Silver PA. 7The yeast mRNA-binding protein Npl3p interacts with the cap-binding complex. J Biol Chem. 2000 Aug 4;275(31):23718-24. PMID:10823828 doi:http://dx.doi.org/10.1074/jbc.M002312200
- ↑ Baron-Benhamou J, Fortes P, Inada T, Preiss T, Hentze MW. The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeast. RNA. 2003 Jun;9(6):654-62. PMID:12756324
- ↑ Kushner DB, Lindenbach BD, Grdzelishvili VZ, Noueiry AO, Paul SM, Ahlquist P. Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15764-9. Epub 2003 Dec 11. PMID:14671320 doi:10.1073/pnas.2536857100
- ↑ Gao Q, Das B, Sherman F, Maquat LE. Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4258-63. Epub 2005 Mar 7. PMID:15753296 doi:http://dx.doi.org/10.1073/pnas.0500684102
- ↑ Kuai L, Das B, Sherman F. A nuclear degradation pathway controls the abundance of normal mRNAs in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13962-7. Epub 2005 Sep 15. PMID:16166263 doi:http://dx.doi.org/10.1073/pnas.0506518102
- ↑ Colot HV, Stutz F, Rosbash M. The yeast splicing factor Mud13p is a commitment complex component and corresponds to CBP20, the small subunit of the nuclear cap-binding complex. Genes Dev. 1996 Jul 1;10(13):1699-708. doi: 10.1101/gad.10.13.1699. PMID:8682299 doi:http://dx.doi.org/10.1101/gad.10.13.1699
- ↑ Lewis JD, Gorlich D, Mattaj IW. A yeast cap binding protein complex (yCBC) acts at an early step in pre-mRNA splicing. Nucleic Acids Res. 1996 Sep 1;24(17):3332-6. PMID:8811086
- ↑ Gorlich D, Kraft R, Kostka S, Vogel F, Hartmann E, Laskey RA, Mattaj IW, Izaurralde E. Importin provides a link between nuclear protein import and U snRNA export. Cell. 1996 Oct 4;87(1):21-32. PMID:8858145
- ↑ McKee AH, Kleckner N. Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3. Genetics. 1997 Jul;146(3):817-34. PMID:9215889
- ↑ Zhang D, Rosbash M. Identification of eight proteins that cross-link to pre-mRNA in the yeast commitment complex. Genes Dev. 1999 Mar 1;13(5):581-92. PMID:10072386
- ↑ Du H, Rosbash M. The U1 snRNP protein U1C recognizes the 5' splice site in the absence of base pairing. Nature. 2002 Sep 5;419(6902):86-90. PMID:12214237 doi:http://dx.doi.org/10.1038/nature00947
- ↑ Tang J, Abovich N, Fleming ML, Seraphin B, Rosbash M. Identification and characterization of a yeast homolog of U1 snRNP-specific protein C. EMBO J. 1997 Jul 1;16(13):4082-91. PMID:9233817 doi:http://dx.doi.org/10.1093/emboj/16.13.4082
- ↑ Liao XC, Tang J, Rosbash M. An enhancer screen identifies a gene that encodes the yeast U1 snRNP A protein: implications for snRNP protein function in pre-mRNA splicing. Genes Dev. 1993 Mar;7(3):419-28. PMID:8449403
- ↑ Tang J, Rosbash M. Characterization of yeast U1 snRNP A protein: identification of the N-terminal RNA binding domain (RBD) binding site and evidence that the C-terminal RBD functions in splicing. RNA. 1996 Oct;2(10):1058-70. PMID:8849781
- ↑ Fortes P, Bilbao-Cortes D, Fornerod M, Rigaut G, Raymond W, Seraphin B, Mattaj IW. Luc7p, a novel yeast U1 snRNP protein with a role in 5' splice site recognition. Genes Dev. 1999 Sep 15;13(18):2425-38. PMID:10500099
- ↑ Alexieva KI, Klis F, Wedler H, Wambutt R, Venkov P. Identification of the essential EPE1 gene involved in retention of secreted proteins on the cell surface of Saccharomyces cerevisiae cells. Int J Biochem Cell Biol. 1999 Sep;31(9):903-14. PMID:10533282
- ↑ Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature. 1999 Sep 9;401(6749):177-80. PMID:10490028 doi:http://dx.doi.org/10.1038/43694
- ↑ Rymond BC. Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):848-52. PMID:8430095
- ↑ Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature. 1999 Sep 9;401(6749):177-80. PMID:10490028 doi:http://dx.doi.org/10.1038/43694
- ↑ Roy J, Zheng B, Rymond BC, Woolford JL Jr. Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins. Mol Cell Biol. 1995 Jan;15(1):445-55. PMID:7799953
- ↑ Bordonne R, Tarassov I. The yeast SME1 gene encodes the homologue of the human E core protein. Gene. 1996 Oct 17;176(1-2):111-7. PMID:8918241
- ↑ Fortes P, Kufel J, Fornerod M, Polycarpou-Schwarz M, Lafontaine D, Tollervey D, Mattaj IW. Genetic and physical interactions involving the yeast nuclear cap-binding complex. Mol Cell Biol. 1999 Oct;19(10):6543-53. PMID:10490594
- ↑ Das B, Guo Z, Russo P, Chartrand P, Sherman F. The role of nuclear cap binding protein Cbc1p of yeast in mRNA termination and degradation. Mol Cell Biol. 2000 Apr;20(8):2827-38. PMID:10733586
- ↑ Shen EC, Stage-Zimmermann T, Chui P, Silver PA. 7The yeast mRNA-binding protein Npl3p interacts with the cap-binding complex. J Biol Chem. 2000 Aug 4;275(31):23718-24. PMID:10823828 doi:http://dx.doi.org/10.1074/jbc.M002312200
- ↑ Baron-Benhamou J, Fortes P, Inada T, Preiss T, Hentze MW. The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeast. RNA. 2003 Jun;9(6):654-62. PMID:12756324
- ↑ Das B, Butler JS, Sherman F. Degradation of normal mRNA in the nucleus of Saccharomyces cerevisiae. Mol Cell Biol. 2003 Aug;23(16):5502-15. PMID:12897126
- ↑ Kushner DB, Lindenbach BD, Grdzelishvili VZ, Noueiry AO, Paul SM, Ahlquist P. Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15764-9. Epub 2003 Dec 11. PMID:14671320 doi:10.1073/pnas.2536857100
- ↑ Uemura H, Jigami Y. GCR3 encodes an acidic protein that is required for expression of glycolytic genes in Saccharomyces cerevisiae. J Bacteriol. 1992 Sep;174(17):5526-32. PMID:1512188
- ↑ Gao Q, Das B, Sherman F, Maquat LE. Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4258-63. Epub 2005 Mar 7. PMID:15753296 doi:http://dx.doi.org/10.1073/pnas.0500684102
- ↑ Kuai L, Das B, Sherman F. A nuclear degradation pathway controls the abundance of normal mRNAs in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13962-7. Epub 2005 Sep 15. PMID:16166263 doi:http://dx.doi.org/10.1073/pnas.0506518102
- ↑ Lewis JD, Gorlich D, Mattaj IW. A yeast cap binding protein complex (yCBC) acts at an early step in pre-mRNA splicing. Nucleic Acids Res. 1996 Sep 1;24(17):3332-6. PMID:8811086
- ↑ Uemura H, Pandit S, Jigami Y, Sternglanz R. Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics. 1996 Apr;142(4):1095-103. PMID:8846890
- ↑ Gorlich D, Kraft R, Kostka S, Vogel F, Hartmann E, Laskey RA, Mattaj IW, Izaurralde E. Importin provides a link between nuclear protein import and U snRNA export. Cell. 1996 Oct 4;87(1):21-32. PMID:8858145
- ↑ Shen EC, Henry MF, Weiss VH, Valentini SR, Silver PA, Lee MS. Arginine methylation facilitates the nuclear export of hnRNP proteins. Genes Dev. 1998 Mar 1;12(5):679-91. PMID:9499403
- ↑ Libri D, Duconge F, Levy L, Vinauger M. A role for the Psi-U mismatch in the recognition of the 5' splice site of yeast introns by the U1 small nuclear ribonucleoprotein particle. J Biol Chem. 2002 May 17;277(20):18173-81. doi: 10.1074/jbc.M112460200. Epub 2002, Mar 4. PMID:11877437 doi:http://dx.doi.org/10.1074/jbc.M112460200
- ↑ Kotovic KM, Lockshon D, Boric L, Neugebauer KM. Cotranscriptional recruitment of the U1 snRNP to intron-containing genes in yeast. Mol Cell Biol. 2003 Aug;23(16):5768-79. PMID:12897147
- ↑ McLean MR, Rymond BC. Yeast pre-mRNA splicing requires a pair of U1 snRNP-associated tetratricopeptide repeat proteins. Mol Cell Biol. 1998 Jan;18(1):353-60. PMID:9418882
- ↑ Abovich N, Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403-12. PMID:9150140
- ↑ Morris DP, Greenleaf AL. The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem. 2000 Dec 22;275(51):39935-43. PMID:10978320 doi:10.1074/jbc.M004118200
- ↑ Murphy MW, Olson BL, Siliciano PG. The yeast splicing factor Prp40p contains functional leucine-rich nuclear export signals that are essential for splicing. Genetics. 2004 Jan;166(1):53-65. PMID:15020406
- ↑ Li X, Liu S, Zhang L, Issaian A, Hill RC, Espinosa S, Shi S, Cui Y, Kappel K, Das R, Hansen KC, Zhou ZH, Zhao R. A unified mechanism for intron and exon definition and back-splicing. Nature. 2019 Sep;573(7774):375-380. doi: 10.1038/s41586-019-1523-6. Epub 2019 Sep, 4. PMID:31485080 doi:http://dx.doi.org/10.1038/s41586-019-1523-6
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