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Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA.
Genes Dev. 1990 Jan; 4(1):98-110.GD

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.

Authors+Show Affiliations

Cold Spring Harbor Laboratory, New York 11724.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

2307372

Citation

Helfman, D M., et al. "Identification of Two Distinct Intron Elements Involved in Alternative Splicing of Beta-tropomyosin Pre-mRNA." Genes & Development, vol. 4, no. 1, 1990, pp. 98-110.
Helfman DM, Roscigno RF, Mulligan GJ, et al. Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. Genes Dev. 1990;4(1):98-110.
Helfman, D. M., Roscigno, R. F., Mulligan, G. J., Finn, L. A., & Weber, K. S. (1990). Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. Genes & Development, 4(1), 98-110.
Helfman DM, et al. Identification of Two Distinct Intron Elements Involved in Alternative Splicing of Beta-tropomyosin Pre-mRNA. Genes Dev. 1990;4(1):98-110. PubMed PMID: 2307372.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of two distinct intron elements involved in alternative splicing of beta-tropomyosin pre-mRNA. AU - Helfman,D M, AU - Roscigno,R F, AU - Mulligan,G J, AU - Finn,L A, AU - Weber,K S, PY - 1990/1/1/pubmed PY - 1990/1/1/medline PY - 1990/1/1/entrez SP - 98 EP - 110 JF - Genes & development JO - Genes Dev VL - 4 IS - 1 N2 - 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. SN - 0890-9369 UR - https://www.unboundmedicine.com/medline/citation/2307372/Identification_of_two_distinct_intron_elements_involved_in_alternative_splicing_of_beta_tropomyosin_pre_mRNA_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=2307372 DB - PRIME DP - Unbound Medicine ER -