| Structural highlightsFunctionSNW1_HUMAN Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. Functions as a splicing factor in pre-mRNA splicing. Is required in the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
Publication Abstract from PubMed
The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B(act) spliceosome at 3.4 A resolution. In the B(act) state, the spliceosome is activated but not catalytically primed, so that it is functionally blocked prior to the first catalytic step of splicing. The spliceosomal core is similar to the yeast B(act) spliceosome; important differences include the presence of the RNA helicase aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior of the purified spliceosome, we developed a principal component analysis-based approach. Calculating the energy landscape revealed eight major conformational states, which we refined to higher resolution. Conformational differences of the highly flexible structural components between these eight states reveal how spliceosomal components contribute to the assembly of the spliceosome, allowing it to generate a dynamic interaction network required for its subsequent catalytic activation.
Structure and Conformational Dynamics of the Human Spliceosomal B(act) Complex.,Haselbach D, Komarov I, Agafonov DE, Hartmuth K, Graf B, Dybkov O, Urlaub H, Kastner B, Luhrmann R, Stark H Cell. 2018 Jan 25;172(3):454-464.e11. doi: 10.1016/j.cell.2018.01.010. Epub 2018 , Jan 17. PMID:29361316[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See AlsoReferences
- ↑ Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD. A role for SKIP in EBNA2 activation of CBF1-repressed promoters. J Virol. 2000 Feb;74(4):1939-47. PMID:10644367
- ↑ Leong GM, Subramaniam N, Figueroa J, Flanagan JL, Hayman MJ, Eisman JA, Kouzmenko AP. Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription. J Biol Chem. 2001 May 25;276(21):18243-8. Epub 2001 Mar 6. PMID:11278756 doi:http://dx.doi.org/10.1074/jbc.M010815200
- ↑ Kim YJ, Noguchi S, Hayashi YK, Tsukahara T, Shimizu T, Arahata K. The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding protein 2, interacts with SKIP and stimulates muscle-specific gene expression. Hum Mol Genet. 2001 May 15;10(11):1129-39. PMID:11371506
- ↑ Zhang C, Baudino TA, Dowd DR, Tokumaru H, Wang W, MacDonald PN. Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription. J Biol Chem. 2001 Nov 2;276(44):40614-20. Epub 2001 Aug 20. PMID:11514567 doi:http://dx.doi.org/10.1074/jbc.M106263200
- ↑ Zhang C, Dowd DR, Staal A, Gu C, Lian JB, van Wijnen AJ, Stein GS, MacDonald PN. Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. J Biol Chem. 2003 Sep 12;278(37):35325-36. Epub 2003 Jul 2. PMID:12840015 doi:http://dx.doi.org/10.1074/jbc.M305191200
- ↑ Leong GM, Subramaniam N, Issa LL, Barry JB, Kino T, Driggers PH, Hayman MJ, Eisman JA, Gardiner EM. Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. Biochem Biophys Res Commun. 2004 Mar 19;315(4):1070-6. PMID:14985122 doi:http://dx.doi.org/10.1016/j.bbrc.2004.02.004
- ↑ Figueroa JD, Hayman MJ. The human Ski-interacting protein functionally substitutes for the yeast PRP45 gene. Biochem Biophys Res Commun. 2004 Jul 9;319(4):1105-9. PMID:15194481 doi:http://dx.doi.org/10.1016/j.bbrc.2004.05.096
- ↑ Bres V, Gomes N, Pickle L, Jones KA. A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat. Genes Dev. 2005 May 15;19(10):1211-26. PMID:15905409 doi:http://dx.doi.org/10.1101/gad.1291705
- ↑ Bracken CP, Wall SJ, Barre B, Panov KI, Ajuh PM, Perkins ND. Regulation of cyclin D1 RNA stability by SNIP1. Cancer Res. 2008 Sep 15;68(18):7621-8. doi: 10.1158/0008-5472.CAN-08-1217. PMID:18794151 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-1217
- ↑ Bres V, Yoshida T, Pickle L, Jones KA. SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation. Mol Cell. 2009 Oct 9;36(1):75-87. doi: 10.1016/j.molcel.2009.08.015. PMID:19818711 doi:http://dx.doi.org/10.1016/j.molcel.2009.08.015
- ↑ Vasquez-Del Carpio R, Kaplan FM, Weaver KL, VanWye JD, Alves-Guerra MC, Robbins DJ, Capobianco AJ. Assembly of a Notch transcriptional activation complex requires multimerization. Mol Cell Biol. 2011 Apr;31(7):1396-408. doi: 10.1128/MCB.00360-10. Epub 2011 Jan , 18. PMID:21245387 doi:http://dx.doi.org/10.1128/MCB.00360-10
- ↑ Chen Y, Zhang L, Jones KA. SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing. Genes Dev. 2011 Apr 1;25(7):701-16. doi: 10.1101/gad.2002611. PMID:21460037 doi:http://dx.doi.org/10.1101/gad.2002611
- ↑ Baudino TA, Kraichely DM, Jefcoat SC Jr, Winchester SK, Partridge NC, MacDonald PN. Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription. J Biol Chem. 1998 Jun 26;273(26):16434-41. PMID:9632709
- ↑ Haselbach D, Komarov I, Agafonov DE, Hartmuth K, Graf B, Dybkov O, Urlaub H, Kastner B, Luhrmann R, Stark H. Structure and Conformational Dynamics of the Human Spliceosomal B(act) Complex. Cell. 2018 Jan 25;172(3):454-464.e11. doi: 10.1016/j.cell.2018.01.010. Epub 2018 , Jan 17. PMID:29361316 doi:http://dx.doi.org/10.1016/j.cell.2018.01.010
|