Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF

Mayeda, A., Helfman, D. M., Krainer, A. R. (May 1993) Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF. Molecular and Cellular Biology, 13 (5). pp. 2993-3001. ISSN 0270-7306 (Print)0270-7306

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URL: http://www.ncbi.nlm.nih.gov/pubmed/8474457
DOI: 10.1128/MCB.13.5.2993

Abstract

The essential splicing factor SF2/ASF and the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) modulate alternative splicing in vitro of pre-mRNAs that contain 5' splice sites of comparable strengths competing for a common 3' splice site. Using natural and model pre-mRNAs, we have examined whether the ratio of SF2/ASF to hnRNP A1 also regulates other modes of alternative splicing in vitro. We found that an excess of SF2/ASF effectively prevents inappropriate exon skipping and also influences the selection of mutually exclusive tissue-specific exons in natural beta-tropomyosin pre-mRNA. In contrast, an excess of hnRNP A1 does not cause inappropriate exon skipping in natural constitutively or alternatively spliced pre-mRNAs. Although hnRNP A1 can promote alternative exon skipping, this effect is not universal and is dependent, e.g., on the size of the internal alternative exon and on the strength of the polypyrimidine tract in the preceding intron. With appropriate alternative exons, an excess of SF2/ASF promotes exon inclusion, whereas an excess of hnRNP A1 causes exon skipping. We propose that in some cases the ratio of SF2/ASF to hnRNP A1 may play a role in regulating alternative splicing by exon inclusion or skipping through the antagonistic effects of these proteins on alternative splice site selection.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Nucleus/metabolism Cell-Free System *Exons Globins/*genetics HeLa Cells *Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoproteins Humans Nuclear Proteins/isolation & purification/*metabolism RNA Precursors/*metabolism *RNA Splicing RNA, Heterogeneous Nuclear/*metabolism RNA-Binding Proteins Rabbits Recombinant Proteins/metabolism Ribonucleoproteins/*metabolism Spliceosomes/*metabolism Tropomyosin/*genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon skipping
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > nuclear ribonucleoprotein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: May 1993
Date Deposited: 11 Mar 2014 20:20
Last Modified: 11 Mar 2014 20:20
PMCID: PMC359692
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29600

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