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PMID: 16109373 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex.

Molecular cell ·Vol. 19 ·No. 4 ·2005-08-19 ·Pages 485-96

Sharma S, Falick AM, Black DL

Abstract

Polypyrimidine tract binding protein (PTB) represses some alternatively spliced exons by direct occlusion of splice sites. In repressing the splicing of the c-src N1 exon, we find that PTB acts by a different mechanism. PTB does not interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents formation of the prespliceosomal early (E) complex across the intervening intron by preventing the assembly of the splicing factor U2AF on the 3' splice site of exon 4. When the unregulated 5' splice site of the upstream exon 3 is present, U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites, PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex. This mechanism likely occurs in many other alternative exons.

MeSH Terms
5' Untranslated Regions/metabolism Alternative Splicing Base Sequence Gene Expression Regulation HeLa Cells Humans Introns Macromolecular Substances/metabolism Models, Molecular Molecular Sequence Data Nuclear Proteins/metabolism Polypyrimidine Tract-Binding Protein/physiology Ribonucleoprotein, U1 Small Nuclear/metabolism Ribonucleoproteins/metabolism Spliceosomes/metabolism Splicing Factor U2AF
Chemicals
5' Untranslated Regions Macromolecular Substances Nuclear Proteins Ribonucleoprotein, U1 Small Nuclear Ribonucleoproteins Splicing Factor U2AF U2AF2 protein, human Polypyrimidine Tract-Binding Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sharma Shalini
Howard Hughes Medical Institute, University of California, Los Angeles, MRL5-748, Charles E. Young Drive South, Los Angeles, California 90095, USA.
Falick Arnold M
Black Douglas L
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2005.07.014
Published
2005-08-19
Pages
485-96
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC1635971
Subset
IM
Grants
NIGMS NIH HHS · R01 GM049662 · United States
NIGMS NIH HHS · R01 GM 49662 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2005.07.014 PMC Full Text View journal details
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