title: Post-transcriptional regulation of rat alpha cardiac myosin heavy chain gene expression.
abstract: The cardiac myosin heavy chain genes, alpha and beta, have been shown to change their patterns of expression rapidly and dramatically in response to a variety of stimuli. A major means of achieving these changes in gene expression is transcriptional control; however, the role of post-transcriptional regulation in cardiac myosin gene expression has not been investigated. We have identified two post-transcriptional events in rat alpha cardiac myosin heavy chain (alpha-MHC) gene expression and investigated their regulatory significance in different developmental and thyroid hormone states. The polyadenylation of alpha-MHC mRNA occurs at three different sites: 12, 18, and 23 bases downstream from a single polyadenylation signal. Hyperthyroid hearts did not demonstrate any change in the proportion of the three alpha-MHC mRNA subspecies. Hypothyroid hearts (which have a decreased amount of total alpha-MHC mRNA) showed a significant increase in the proportion of the longest subspecies and a decrease in the shortest subspecies. The second post-transcriptional event in alpha-MHC gene expression which was demonstrated was the inclusion or exclusion of a codon, CAG, encoding glutamine at position 1931, resulting from alternate splicing of the alpha-MHC transcript. The ratio of CAG+ and CAG- forms of mRNA in the adult euthyroid hearts is 40:60% which was unchanged in hypo- and hyperthyroid states. This is the first example of alternate splicing in a vertebrate sarcomeric myosin heavy chain gene. We conclude that the rat alpha-MHC gene transcript is post-transcriptionally modified.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: R
authors.initials: R
authors.lastname: Sindhwani
authors.forename: F
authors.initials: F
authors.lastname: Ismail-Beigi
authors.forename: L A
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation; D006980:Hyperthyroidism / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis* / Q000235:genetics; D011061:Poly A / Q000032:analysis; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015719:Single-Strand Specific DNA and RNA Endonucleases
chemical_list: D017931:DNA Primers; D015347:RNA Probes; D012333:RNA, Messenger; D011061:Poly A; D015719:Single-Strand Specific DNA and RNA Endonucleases; D009218:Myosins