Analysis of in situ pre-mRNA targets of human splicing factor SF1 reveals a function in alternative splicing

Article Article scientifique Article Analysis of in situ pre-mRNA targets of human splicing factor SF1 reveals a function in alternative splicing eng 2011 author Corioni Margherita 586763 author Antih Nicolas 627157 author Tanackovic Abbas-Terki Goranka 133515 author Zavolan Mihaela author Kraemer Angela 22808 1868-1879 10.1093/nar/gkq1042 21062807 0305-1048 The conserved pre-mRNA splicing factor SF1 is implicated in 3' splice site recognition by binding directly to the intron branch site. However, because SF1 is not essential for constitutive splicing, its role in pre-mRNA processing has remained mysterious. Here, we used crosslinking and immunoprecipitation (CLIP) to analyze short RNAs directly bound by human SF1 in vivo. SF1 bound mainly pre-mRNAs, with 77% of target sites in introns. Binding to target RNAs in vitro was dependent on the newly defined SF1 binding motif ACUNAC, strongly resembling human branch sites. Surprisingly, the majority of SF1 binding sites did not map to the expected position near 3' splice sites. Instead, target sites were distributed throughout introns, and a smaller but significant fraction occurred in exons within coding and untranslated regions. These data suggest a more complex role for SF1 in splicing regulation. Indeed, SF1 silencing affected alternative splicing of endogenous transcripts, establishing a previously unexpected role for SF1 and branch site-like sequences in splice site selection. Alternative Splicing Base Sequence Binding Sites DNA-Binding Proteins/antagonists & inhibitors/metabolism/physiology Genome, Human Hela Cells Humans Molecular Sequence Data Nuclear Proteins/metabolism RNA Interference RNA Precursors/isolation & purification/metabolism RNA, Messenger/isolation & purification/metabolism RNA-Binding Proteins/antagonists & inhibitors/metabolism/physiology Ribonucleoproteins/metabolism Transcription Factors/antagonists & inhibitors/metabolism/physiology Dewey 570 46 Département de biologie cellulaire 165 false Nucleic acids research 39 5 4fb214d9-40cd-4997-a6a0-9d48f2d7a863 Article (Published version) Public 2011_Corioni_NAR_incl_suppl.pdf 985504 application/pdf openAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire

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Analysis of in situ pre-mRNA targets of human splicing factor SF1 reveals a function in alternative splicing	Nucleic acids research			2011	646	1,515

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Corioni, Margherita