Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.

The alpha-actinin gene has a pair of alternatively spliced exons. The smooth muscle (SM) exon is repressed in most cell types by polypyrimidine tract binding protein (PTB). CELF (CUG-BP and ETR3-like factors) family proteins, splicing regulators whose activities are altered in myotonic dystrophy, we...

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Main Authors: Gromak, N, Matlin, A, Cooper, T, Smith, C
Format: Journal article
Language:English
Published: 2003
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author Gromak, N
Matlin, A
Cooper, T
Smith, C
author_facet Gromak, N
Matlin, A
Cooper, T
Smith, C
author_sort Gromak, N
collection OXFORD
description The alpha-actinin gene has a pair of alternatively spliced exons. The smooth muscle (SM) exon is repressed in most cell types by polypyrimidine tract binding protein (PTB). CELF (CUG-BP and ETR3-like factors) family proteins, splicing regulators whose activities are altered in myotonic dystrophy, were found to coordinately regulate selection of the two alpha-actinin exons. CUG-BP and ETR3 activated the SM exon, and along with CELF4 they were also able to repress splicing of the NM (nonmuscle) exon both in vivo and in vitro. Activation of SM exon splicing was associated with displacement of PTB from the polypyrimidine tract by binding of CUG-BP at adjacent sites. Our data provides direct evidence for the activity of CELF proteins as both activators and repressors of splicing within a single-model system of alternative splicing, and suggests a model whereby alpha-actinin alternative splicing is regulated by synergistic and antagonistic interactions between members of the CELF and PTB families.
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spelling oxford-uuid:782fccd5-1c19-4920-ade9-938023a22e952022-03-26T20:28:58ZAntagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:782fccd5-1c19-4920-ade9-938023a22e95EnglishSymplectic Elements at Oxford2003Gromak, NMatlin, ACooper, TSmith, CThe alpha-actinin gene has a pair of alternatively spliced exons. The smooth muscle (SM) exon is repressed in most cell types by polypyrimidine tract binding protein (PTB). CELF (CUG-BP and ETR3-like factors) family proteins, splicing regulators whose activities are altered in myotonic dystrophy, were found to coordinately regulate selection of the two alpha-actinin exons. CUG-BP and ETR3 activated the SM exon, and along with CELF4 they were also able to repress splicing of the NM (nonmuscle) exon both in vivo and in vitro. Activation of SM exon splicing was associated with displacement of PTB from the polypyrimidine tract by binding of CUG-BP at adjacent sites. Our data provides direct evidence for the activity of CELF proteins as both activators and repressors of splicing within a single-model system of alternative splicing, and suggests a model whereby alpha-actinin alternative splicing is regulated by synergistic and antagonistic interactions between members of the CELF and PTB families.
spellingShingle Gromak, N
Matlin, A
Cooper, T
Smith, C
Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title_full Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title_fullStr Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title_full_unstemmed Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title_short Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein.
title_sort antagonistic regulation of alpha actinin alternative splicing by celf proteins and polypyrimidine tract binding protein
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AT coopert antagonisticregulationofalphaactininalternativesplicingbycelfproteinsandpolypyrimidinetractbindingprotein
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