| Structural highlights
Function
[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.[1] [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.[2] [3] [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.[4] [5] [RDS3_YEAST] Required for pre-mRNA splicing. Involved in regulation of drug sensitivity and may play a role in multidrug resistance.[6] [7] [PRP9_YEAST] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [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.[8] [9] [HSH49_YEAST] Possible SF3b-like factor. [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.[10] [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. [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. [RSE1_YEAST] Involved in G2/M transition (By similarity). Required for pre-mRNA splicing and endoplasmic reticulum (ER) to Golgi secretion pathway. U2 snRNPs associated protein required for the pre-spliceosome assembly. The involvement in ER to Golgi secretion is probably indirect and due to the splicing of the pre-mRNA coding for SAR1, a small GTP-binding protein required for COPII vesicle formation from the ER.[11] [12] [PRP21_YEAST] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for binding of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly. [YSF3_YEAST] Involved in pre-mRNA splicing. Required for the SF3b integrity and prespliceosome assembly.[13] [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.[14] [15] [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. [SF3B1_YEAST] Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. [MSL1_YEAST] Involved in pre-mRNA splicing. This protein is associated with snRNP U2. It binds stem loop IV of U2 snRNA.[16] [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. [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. [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.[17] [18] [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. [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.[19] [CUS1_YEAST] Essential splicing protein required for U2 snRNP binding to pre-mRNA during spliceosome assembly. [NAM8_YEAST] Acts as a suppressor of mitochondrial splicing deficiencies when overexpressed. Could be a non-essential component of the mitochondrial splicing machinery. [RU17_YEAST] Involved in nuclear mRNA splicing. [PRP11_YEAST] mRNA splicing factors, PRP9, PRP11, and PRP21, are necessary for addition of the U2 snRNP to the pre-mRNA in an early step of spliceosome assembly.[20] [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.[21] [22] [23]
Publication Abstract from PubMed
The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors(1). For branching, the intron 5' splice site and the branch point sequence are selected and brought by the U1 and U2 snRNPs into the prespliceosome(1), which is a focal point for regulation by alternative splicing factors(2). The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome. Recent studies have revealed the structural basis of the branching and exon-ligation reactions(3), however, the structural basis of the early events in spliceosome assembly remains poorly understood(4). Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae prespliceosome at near-atomic resolution. The structure reveals an induced stabilization of the 5' splice site in the U1 snRNP, and provides structural insights into the functions of the human alternative splicing factors LUC7-like (yeast Luc7) and TIA-1 (yeast Nam8), both of which have been linked to human disease(5,6). In the prespliceosome, the U1 snRNP associates with the U2 snRNP through a stable contact with the U2 3' domain and a transient yeast-specific contact with the U2 SF3b-containing 5' region, leaving its tri-snRNP-binding interface fully exposed. The results suggest mechanisms for 5' splice site transfer to the U6 ACAGAGA region within the assembled spliceosome and for its subsequent conversion to the activation-competent B-complex spliceosome(7,8). Taken together, the data provide a working model to investigate the early steps of spliceosome assembly.
Prespliceosome structure provides insights into spliceosome assembly and regulation.,Plaschka C, Lin PC, Charenton C, Nagai K Nature. 2018 Jul;559(7714):419-422. doi: 10.1038/s41586-018-0323-8. Epub 2018 Jul, 11. PMID:29995849[24]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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:http://dx.doi.org/10.1093/emboj/17.21.6348
- ↑ 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
- ↑ 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
- ↑ Akache B, Turcotte B. New regulators of drug sensitivity in the family of yeast zinc cluster proteins. J Biol Chem. 2002 Jun 14;277(24):21254-60. Epub 2002 Apr 9. PMID:11943786 doi:http://dx.doi.org/10.1074/jbc.M202566200
- ↑ Wang Q, Rymond BC. Rds3p is required for stable U2 snRNP recruitment to the splicing apparatus. Mol Cell Biol. 2003 Oct;23(20):7339-49. PMID:14517302
- ↑ 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
- ↑ 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
- ↑ Caspary F, Shevchenko A, Wilm M, Seraphin B. Partial purification of the yeast U2 snRNP reveals a novel yeast pre-mRNA splicing factor required for pre-spliceosome assembly. EMBO J. 1999 Jun 15;18(12):3463-74. PMID:10369685 doi:http://dx.doi.org/10.1093/emboj/18.12.3463
- ↑ Chen EJ, Frand AR, Chitouras E, Kaiser CA. A link between secretion and pre-mRNA processing defects in Saccharomyces cerevisiae and the identification of a novel splicing gene, RSE1. Mol Cell Biol. 1998 Dec;18(12):7139-46. PMID:9819400
- ↑ Wang Q, He J, Lynn B, Rymond BC. Interactions of the yeast SF3b splicing factor. Mol Cell Biol. 2005 Dec;25(24):10745-54. PMID:16314500 doi:http://dx.doi.org/25/24/10745
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Yan D, Perriman R, Igel H, Howe KJ, Neville M, Ares M Jr. CUS2, a yeast homolog of human Tat-SF1, rescues function of misfolded U2 through an unusual RNA recognition motif. Mol Cell Biol. 1998 Sep;18(9):5000-9. PMID:9710584
- ↑ 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
- ↑ Plaschka C, Lin PC, Charenton C, Nagai K. Prespliceosome structure provides insights into spliceosome assembly and regulation. Nature. 2018 Jul;559(7714):419-422. doi: 10.1038/s41586-018-0323-8. Epub 2018 Jul, 11. PMID:29995849 doi:http://dx.doi.org/10.1038/s41586-018-0323-8
|
