Post-transcriptional regulation of rat α cardiac myosin heavy chain gene expression

The cardiac myosin heavy chain genes, α and β, 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 α cardiac myosin heavy chain (α-MHC) gene expression and investigated their regulatory significance in different developmental and thyroid hormone states. The polyadenylation of α-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 α-MHC mRNA subspecies. Hypothyroid hearts (which have a decreased amount of total α-MHC mRNA) showed a significant increase in the proportion of the longest subspecies and a decrease in the shortest subspecies. The second posttranscriptional event in α-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 α-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 α-MHC gene transcript is post- transcriptionally modified.