Three novel brain tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene through the use of alternative promoters and alternative RNA processing

Lees-Miller, J. P., Goodwin, L. O., Helfman, D. M. (April 1990) Three novel brain tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene through the use of alternative promoters and alternative RNA processing. Mol Cell Biol, 10 (4). pp. 1729-42. ISSN 0270-7306 (Print)0270-7306 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/2320008
DOI: 10.1128/MCB.10.4.1729

Abstract

cDNA clones encoding three novel tropomyosins, termed TMBr-1, TMBr-2, and TMBr-3, were isolated and characterized from a rat brain cDNA library. All are derived from a single gene, which was previously found to express striated muscle alpha-tropomyosin and a number of other tropomyosin isoforms via an alternative splicing mechanism (N. Ruiz-Opazo and B. Nadal-Ginard, J. Biol. Chem. 262:4755-4765, 1987; D. F. Wieczorek, C. W. J. Smith, and B. Nadal-Ginard, Mol. Cell. Biol. 8:679-694, 1988). The derived amino acid sequences revealed that TMBr-1 contains 281 amino acids, TMBr-2 contains 251 amino acids, and TMBr-3 contains 245 amino acids. All three proteins contain a region that is identical to amino acids 81 through 258 of skeletal muscle alpha-tropomyosin. TMBr-1 is identical to striated muscle alpha-tropomyosin from amino acids 1 through 258 but contains a novel COOH-terminal region from amino acids 259 through 281. TMBr-2 and TMBr-3 both contain identical NH2-terminal sequences from amino acids 1 through 44 which were found to be expressed from a novel promoter. TMBr-3 contains the same COOH-terminal region as TMBr-1, whereas TMBr-2 contains a second novel COOH-terminal region. The genomic organization of the exons encoding TMBr-1, TMBr-2, and TMBr-3 were determined. These studies revealed a previously uncharacterized promoter located in the internal region of the alpha-TM gene as well as two novel COOH-terminal coding exons. The alpha-TM gene is a complex transcription unit containing 15 exons including two alternative promoters, two internal mutually exclusive exon cassettes, and four alternatively spliced 3' exons that encode four different COOH-terminal coding regions. A total of nine distinct mRNAs are known to be expressed from the alpha-TM gene in a cell type-specific manner in tissues such as striated muscle, smooth muscle, kidney, liver, brain, and fibroblasts. The mRNAs encoding TMBr-1, TMBr-2, and TMBr-3 were found to be expressed only in brain tissue, with TMBr-3 being expressed at much greater levels than TMBr-1 and TMBr-2. The individual structural characteristics of each brain alpha-tropomyosin isoform and their possible functions are discussed.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Base Sequence Brain/*metabolism Cloning, Molecular Exons Gene Library *Genes Genetic Variation Introns Molecular Sequence Data Plasmids *Promoter Regions, Genetic *RNA Splicing RNA, Messenger/genetics Rats Restriction Mapping Sequence Homology, Nucleic Acid *Transcription, Genetic 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 > DNA expression > promoter
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
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: April 1990
Date Deposited: 09 Feb 2016 20:55
Last Modified: 09 Feb 2016 20:55
PMCID: PMC362279
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32348

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