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PMID: 11421360 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB).

RNA (New York, N.Y.) ·Vol. 7 ·No. 6 ·2001-06-00 ·Pages 819-32

Wollerton MC, Gooding C, Robinson F, Brown EC, Jackson RJ, Smith CW

Abstract

Polypyrimidine tract binding protein (PTB) is an RNA-binding protein that regulates splicing by repressing specific splicing events. It also has roles in 3'-end processing, internal initiation of translation, and RNA localization. PTB exists in three alternatively spliced isoforms, PTB1, PTB2, and PTB4, which differ by the insertion of 19 or 26 amino acids, respectively, between the second and third RNA recognition motif domains. Here we show that the PTB isoforms have distinct activities upon alpha-tropomyosin (TM) alternative splicing. PTB1 reduced the repression of TM exon 3 in transfected smooth muscle cells, whereas PTB4 enhanced TM exon 3 skipping in vivo and in vitro. PTB2 had an intermediate effect. The PTB4 > PTB2 > PTB1 repressive hierarchy was observed in all in vivo and in vitro assays with TM, but the isoforms were equally active in inducing skipping of alpha-actinin exons and showed the opposite hierarchy of activity when tested for activation of IRES-driven translation. These findings establish that the ratio of PTB isoforms could form part of a cellular code that in turn controls the splicing of various other pre-mRNAs.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence Cell Line Exons Molecular Sequence Data Polypyrimidine Tract-Binding Protein Protein Biosynthesis Protein Isoforms/chemistry,genetics,physiology RNA Precursors/chemistry,metabolism RNA, Messenger/chemistry,metabolism RNA-Binding Proteins/chemistry,genetics,physiology Recombinant Proteins/chemistry,genetics,metabolism Ribonucleoproteins/chemistry,genetics,physiology
Chemicals
Protein Isoforms RNA Precursors RNA, Messenger RNA-Binding Proteins Recombinant Proteins Ribonucleoproteins Polypyrimidine Tract-Binding Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wollerton M C
Department of Biochemistry, University of Cambridge, United Kingdom.
Gooding C
Robinson F
Brown E C
Jackson R J
Smith C W
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1355-8382
DOI
10.1017/s1355838201010214
Published
2001-06-00
Pages
819-32
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC1370133
Subset
IM
External Links
PubMed source DOI: 10.1017/s1355838201010214 PMC Full Text View journal details
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