| Structural highlights
Function
[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. [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.[1] [2] [3] [RU17_YEAST] Involved in nuclear mRNA splicing. [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.[4] [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.[5] [6] [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. [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.[7] [8] [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. [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. [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.[9] [10] [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.[11] [12] [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.[13] [14] [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
U1 snRNP plays a critical role in 5'-splice site recognition and is a frequent target of alternative splicing factors. These factors transiently associate with human U1 snRNP and are not amenable for structural studies, while their Saccharomyces cerevisiae (yeast) homologs are stable components of U1 snRNP. Here, we report the cryoEM structure of yeast U1 snRNP at 3.6 A resolution with atomic models for ten core proteins, nearly all essential domains of its RNA, and five stably associated auxiliary proteins. The foot-shaped yeast U1 snRNP contains a core in the "ball-and-toes" region architecturally similar to the human U1 snRNP. All auxiliary proteins are in the "arch-and-heel" region and connected to the core through the Prp42/Prp39 paralogs. Our demonstration that homodimeric human PrpF39 directly interacts with U1C-CTD, mirroring yeast Prp42/Prp39, supports yeast U1 snRNP as a model for understanding how transiently associated auxiliary proteins recruit human U1 snRNP in alternative splicing.
CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing.,Li X, Liu S, Jiang J, Zhang L, Espinosa S, Hill RC, Hansen KC, Zhou ZH, Zhao R Nat Commun. 2017 Oct 19;8(1):1035. doi: 10.1038/s41467-017-01241-9. PMID:29051543[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Li X, Liu S, Jiang J, Zhang L, Espinosa S, Hill RC, Hansen KC, Zhou ZH, Zhao R. CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing. Nat Commun. 2017 Oct 19;8(1):1035. doi: 10.1038/s41467-017-01241-9. PMID:29051543 doi:http://dx.doi.org/10.1038/s41467-017-01241-9
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