Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA

Helfman, D. M., Roscigno, R. F., Mulligan, G. J., Finn, L. A., Weber, K. S. (January 1990) Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. Genes Dev, 4 (1). pp. 98-110. ISSN 0890-9369 (Print)0890-9369 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/2307372
DOI: 10.1101/gad.4.1.98

Abstract

The rat beta-tropomyosin gene encodes two isoforms, termed skeletal muscle beta-tropomyosin and fibroblast last tropomyosim 1 (TM-1), via an alternative RNA processing mechanism. The gene contains 11 exons. Exons 1-5 and exons 8 and 9 are common to all mRNAs expressed from the gene. Exons 6 and 11 are used in fibroblasts, as well as smooth muscle, whereas exons 7 and 10 are used only in skeletal muscle. In the present studies we focused on the mutually exclusive internal alternative splice choice involving exon 6 (fibroblast-type splice) and exon 7 (skeletal muscle-type splice). We have identified two distinct elements in the intron, upstream of exon 7, involved in splice site selection. The first element is comprised of a polypyrimidine tract located 89-143 nucleotides upstream of the 3' splice site, which specifies the location of the lariat branchpoints used, 144-153 nucleotides upstream of exon 7. The 3' splice site AG dinucleotide has no role in selection of these branchpoints. The second element is comprised of intron sequences located between the polypyrimidine tract and the 3' splice site of exon 7. It contains an important determinant in alternative splice site selection, because deletion of these sequences results in the use of the skeletal muscle-specific exon in nonmuscle cells. We propose that the use of lariat branchpoints located far upstream from a 3' splice site may be a general feature of some alternatively excised introns, reflecting the presence of regulatory sequences located between the lariat branch site and the 3' splice site. The data also indicate that alternative splicing of the rat beta-tropomyosin gene is regulated by a somewhat different mechanism from that described for rat alpha-tropomyosin gene and the transformer-2 gene of Drosophila melanogaster.

Item Type: Paper
Uncontrolled Keywords: Animals Base Sequence Exons HeLa Cells Humans *Introns Molecular Sequence Data Muscles/metabolism RNA Precursors/*metabolism *RNA Splicing RNA, Messenger/*metabolism Rats Tropomyosin/*genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > introns
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > tropomyosin
CSHL Authors:
Communities: CSHL labs > Helfman lab
Depositing User: Matt Covey
Date: January 1990
Date Deposited: 29 Mar 2016 15:03
Last Modified: 03 Nov 2017 20:57
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32298

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