Structural highlights
Function
[SF01_HUMAN] Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
During spliceosome assembly, splicing factor 1 (SF1) specifically recognizes the intron branch point sequence (BPS) UACUAAC in the pre-mRNA transcripts. We show that the KH-QUA2 region of SF1 defines an enlarged KH (hn RNP K) fold which is necessary and sufficient for BPS binding. The 3' part of the BPS (UAAC), including the conserved branch point adenosine (underlined), is specifically recognized in a hydrophobic cleft formed by the Gly-Pro-Arg-Gly motif and the variable loop of the KH domain. The QUA2 region recognizes the 5' nucleotides of the BPS (ACU). The branch point adenosine acting as the nucleophile in the first biochemical step of splicing is deeply buried. BPS RNA recognition suggests how SF1 may facilitate subsequent formation of the prespliceosomal complex A.
Structural basis for recognition of the intron branch site RNA by splicing factor 1.,Liu Z, Luyten I, Bottomley MJ, Messias AC, Houngninou-Molango S, Sprangers R, Zanier K, Kramer A, Sattler M Science. 2001 Nov 2;294(5544):1098-102. PMID:11691992[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arning S, Gruter P, Bilbe G, Kramer A. Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996 Aug;2(8):794-810. PMID:8752089
- ↑ Wang X, Bruderer S, Rafi Z, Xue J, Milburn PJ, Kramer A, Robinson PJ. Phosphorylation of splicing factor SF1 on Ser20 by cGMP-dependent protein kinase regulates spliceosome assembly. EMBO J. 1999 Aug 16;18(16):4549-59. PMID:10449420 doi:http://dx.doi.org/10.1093/emboj/18.16.4549
- ↑ Zhang D, Paley AJ, Childs G. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem. 1998 Jul 17;273(29):18086-91. PMID:9660765
- ↑ Liu Z, Luyten I, Bottomley MJ, Messias AC, Houngninou-Molango S, Sprangers R, Zanier K, Kramer A, Sattler M. Structural basis for recognition of the intron branch site RNA by splicing factor 1. Science. 2001 Nov 2;294(5544):1098-102. PMID:11691992 doi:http://dx.doi.org/10.1126/science.1064719
