Cis-Elements Involved in Alternative Splicing in the Rat Beta-Tropomyosin Gene - the 3'-Splice Site of the Skeletal-Muscle Exon-7 Is the Major Site of Blockage in Nonmuscle Cells

Guo, W., Helfman, D. M. (October 1993) Cis-Elements Involved in Alternative Splicing in the Rat Beta-Tropomyosin Gene - the 3'-Splice Site of the Skeletal-Muscle Exon-7 Is the Major Site of Blockage in Nonmuscle Cells. Nucleic Acids Res, 21 (20). pp. 4762-4768. ISSN 0305-1048

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Abstract

We have been using the rat beta-tropomyosin (beta-TM) gene as a model system to study the mechanism of alternative splicing. The beta-TM gene spans 10 kb with 11 exons and encodes two distinct isoforms, namely skeletal muscle beta-TM and fibroblast TM-1. Exons 1 - 5, 8, and 9 are common to all mRNAs expressed from this gene. Exons 6 and 11 are used in fibroblasts, as well as in smooth muscle cells, whereas exons 7 and 1 0 are used exclusively in skeletal muscle cells. Our previous studies localized the critical elements for regulated alternative splicing to sequences within exon 7 and the adjacent upstream intron. We also demonstrated that these sequences function, in part, to regulate splice-site selection in vivo by interacting with cellular factors that block the use of the skeletal muscle exon in nonmuscle cells (1). Here we have further characterized the critical cis-acting elements involved in alternative splice site selection. Our data demonstrate that exon 7 and its flanking intron sequences are sufficient to regulate the suppression of exon 7 in nonmuscle cells when flanked by heterologous exons derived from adenovirus. We have also shown by both in vivo and in vitro assays that the blockage of exon 7 in nonmuscle cells is primarily at its 3'-splice site. A model is presented for regulated alternative splicing in both skeletal muscle and nonmuscle cells.

Item Type: Paper
Uncontrolled Keywords: PRE-MESSENGER-RNA BRANCH POINT LOCATION SEQUENCES INVITRO SELECTION TRANSCRIPTS INVIVO POLYADENYLATION IDENTIFICATION BINDING
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 > exons
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: October 1993
Date Deposited: 08 Apr 2016 18:50
Last Modified: 08 Nov 2017 16:11
PMCID: PMC331503
Related URLs:
URI: https://repository.cshl.edu/id/eprint/32584

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