8233825

pubmed:Citation

20

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 10 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.

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http://linkedlifedata.com/resource/pubmed/journal/0411011

http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Tropomyosin

Oct

pubmed-author:GurRR, pubmed-author:HelfmanD MDM

11

NLM

4762-8

pubmed-meshheading:8233825-Alternative Splicing, pubmed-meshheading:8233825-Animals, pubmed-meshheading:8233825-Base Sequence, pubmed-meshheading:8233825-DNA, pubmed-meshheading:8233825-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:8233825-Exons, pubmed-meshheading:8233825-HeLa Cells, pubmed-meshheading:8233825-Humans, pubmed-meshheading:8233825-Introns, pubmed-meshheading:8233825-Molecular Sequence Data, pubmed-meshheading:8233825-Muscles, pubmed-meshheading:8233825-Mutation, pubmed-meshheading:8233825-Polymerase Chain Reaction, pubmed-meshheading:8233825-Rats, pubmed-meshheading:8233825-Tropomyosin

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.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't