title: Regulation of alternative splicing by the core spliceosomal machinery.
abstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP (small nuclear ribonucleoprotein) protein SmB/B' self-regulates its expression by promoting the inclusion of a highly conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B' in human cells results in reduced levels of snRNPs and a striking reduction in the inclusion levels of hundreds of additional alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA-binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors.
authors.affiliation: Banting and Best Department of Medical Research, The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
authors.forename: Arneet L
authors.initials: AL
authors.lastname: Saltzman
authors.forename: Qun
authors.initials: Q
authors.lastname: Pan
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
mesh_terms: D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology*; D001483:Base Sequence; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics / Q000502:physiology; D050436:Regulatory Elements, Transcriptional / Q000502:physiology; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017381:Spliceosomes / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D055517:snRNP Core Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D017411:Ribonucleoproteins, Small Nuclear; C526407:SNRPB protein, human; C526409:SNRPD1 protein, human; D055517:snRNP Core Proteins