| Structural highlights
Function
[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. [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. [MSL1_YEAST] Involved in pre-mRNA splicing. This protein is associated with snRNP U2. It binds stem loop IV of U2 snRNA.[1] [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.[2] [3] [SLT11_YEAST] Involved in pre-mRNA splicing. Facilitates the cooperative formation of U2/U6 helix II in association with stem II in the spliceosome. Binds to RNA.[4] [5] [PRP45_YEAST] Involved in pre-mRNA splicing. Associated with the spliceosome throughout the splicing reactions, until after the second catalytic step.[6] [7] [RU2A_YEAST] Involved in pre-mRNA splicing. Associates to U2 snRNA in a MSL1 dependent manner and is required for normal accumulation of U2 snRNA. Required for the spliceosome assembly and the efficient addition of U2 snRNP onto the pre-mRNA.[8] [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.[9] [10] [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. [PRP8_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.[11] [12] [13] [14] [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. [SN114_YEAST] Component of the U5 snRNP complex required for pre-mRNA splicing. Binds GTP. [BUD31_YEAST] Involved in pre-mRNA splicing. Important for bud site selection. [CWC25_YEAST] Involved in pre-mRNA splicing.[15] [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.[16] [CWC21_YEAST] Involved in pre-mRNA splicing. May function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome, together with ISY1. May do so by stabilizing the catalytic center or the position of the RNA substrate.[17] [18]
Publication Abstract from PubMed
Pre-mRNA splicing proceeds by two consecutive trans-esterification reactions via a lariat-intron intermediate. We present the 3.8 A cryo-EM structure of the spliceosome immediately after lariat formation. The 5'-splice site is cleaved but remains close to the catalytic Mg2+ site in the U2/U6 snRNA triplex, and the 5'-phosphate of the intron nucleotide G(+1) is linked to the branch adenosine 2'OH. The 5'-exon is held between the Prp8 amino-terminal and Linker domains, and base-pairs with U5 snRNA loop 1. Non-Watson-Crick interactions between the branch helix and 5'-splice site dock the branch adenosine into the active site, while intron nucleotides +3 to +6 base-pair with the U6 snRNA ACAGAGA sequence. Isy1 and the step one factors Yju2 and Cwc25 stabilise docking of the branch helix. The intron downstream of the branch site emerges between the Prp8 reverse transcriptase (RT) and Linker domains and extends towards the Prp16 helicase, suggesting a plausible mechanism of remodelling before exon ligation.
Cryo-EM structure of the spliceosome immediately after branching.,Galej WP, Wilkinson ME, Fica SM, Oubridge C, Newman AJ, Nagai K Nature. 2016 Jul 26. doi: 10.1038/nature19316. PMID:27459055[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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 Jun;16(6):2787-95. PMID:8649387
- ↑ 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:https://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
- ↑ Xu D, Friesen JD. Splicing factor slt11p and its involvement in formation of U2/U6 helix II in activation of the yeast spliceosome. Mol Cell Biol. 2001 Feb;21(4):1011-23. PMID:11158289 doi:https://dx.doi.org/10.1128/MCB.21.4.1011-1023.2001
- ↑ Xu D, Field DJ, Tang SJ, Moris A, Bobechko BP, Friesen JD. Synthetic lethality of yeast slt mutations with U2 small nuclear RNA mutations suggests functional interactions between U2 and U5 snRNPs that are important for both steps of pre-mRNA splicing. Mol Cell Biol. 1998 Apr;18(4):2055-66. PMID:9528778
- ↑ Martinkova K, Lebduska P, Skruzny M, Folk P, Puta F. Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability. J Biochem. 2002 Oct;132(4):557-63. PMID:12359070
- ↑ Albers M, Diment A, Muraru M, Russell CS, Beggs JD. Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors. RNA. 2003 Jan;9(1):138-50. PMID:12554883
- ↑ Caspary F, Seraphin B. The yeast U2A'/U2B complex is required for pre-spliceosome formation. EMBO J. 1998 Nov 2;17(21):6348-58. PMID:9799242 doi:https://dx.doi.org/10.1093/emboj/17.21.6348
- ↑ 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:https://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
- ↑ Jackson SP, Lossky M, Beggs JD. Cloning of the RNA8 gene of Saccharomyces cerevisiae, detection of the RNA8 protein, and demonstration that it is essential for nuclear pre-mRNA splicing. Mol Cell Biol. 1988 Mar;8(3):1067-75. PMID:2835658
- ↑ 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
- ↑ McPheeters DS, 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 Jun;23(12):4174-86. PMID:12773561
- ↑ Yang K, Zhang L, Xu T, Heroux A, Zhao R. Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13817-22. Epub 2008 Sep 8. PMID:18779563
- ↑ Hazbun TR, Malmstrom L, Anderson S, Graczyk BJ, Fox B, Riffle M, Sundin BA, Aranda JD, McDonald WH, Chiu CH, Snydsman BE, Bradley P, Muller EG, Fields S, Baker D, Yates JR 3rd, Davis TN. Assigning function to yeast proteins by integration of technologies. Mol Cell. 2003 Dec;12(6):1353-65. PMID:14690591
- ↑ 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
- ↑ Khanna M, Van Bakel H, Tang X, Calarco JA, Babak T, Guo G, Emili A, Greenblatt JF, Hughes TR, Krogan NJ, Blencowe BJ. A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300. RNA. 2009 Dec;15(12):2174-85. Epub 2009 Sep 29. PMID:19789211 doi:https://dx.doi.org/rna.1790509
- ↑ Grainger RJ, Barrass JD, Jacquier A, Rain JC, Beggs JD. Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome. RNA. 2009 Dec;15(12):2161-73. Epub 2009 Oct 23. PMID:19854871 doi:https://dx.doi.org/rna.1908309
- ↑ Galej WP, Wilkinson ME, Fica SM, Oubridge C, Newman AJ, Nagai K. Cryo-EM structure of the spliceosome immediately after branching. Nature. 2016 Jul 26. doi: 10.1038/nature19316. PMID:27459055 doi:https://dx.doi.org/10.1038/nature19316
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