title: Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting U2 snRNA base-pairing away from the branch point.
abstract: The mouse immunoglobulin (IgM) pre-mRNA contains a splicing inhibitor that bears multiple binding sites for the splicing repressor polypyrimidine tract binding protein (PTB). Here we show that the inhibitor directs assembly of an ATP-dependent complex that contains PTB and U1 and U2 small nuclear RNAs (snRNAs). Unexpectedly, although U2 snRNA is present in the inhibitor complex, it is not base-paired to the branch point. We present evidence that inhibitor-bound PTB contacts U2 snRNA to promote base-pairing to an adjacent branch point-like sequence within the inhibitor, thereby preventing the U2 snRNA-branch point interaction and resulting in splicing repression. Our studies reveal a novel mechanism by which PTB represses splicing.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
authors.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.forename: Huyn Kyung
authors.initials: HK
authors.lastname: Oh
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D020029:Base Pairing / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D047468:Immunoprecipitation; D051379:Mice; D008969:Molecular Sequence Data; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics
chemical_list: D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D012322:RNA Precursors; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; C405483:U1 small nuclear RNA; C405484:U2 small nuclear RNA; D038941:Polypyrimidine Tract-Binding Protein; D000255:Adenosine Triphosphate
keywords: PTB; U2 snRNA; branch point; polypyrimidine tract binding protein; pre-mRNA splicing; splicing inhibitory complex