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.