POSTTRANSCRIPTIONAL REGULATION OF RAT ALPHA-CARDIAC MYOSIN HEAVY-CHAIN GENE-EXPRESSION

The cardiac myosin heavy chain genes, alpha and beta, have been shown to change their patterns of expression rapidly and dramatically in res ponse to a variety of stimuli. A major means of achieving these change s 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 eve nts in rat a cardiac myosin heavy chain (alpha-MHC) gene expression an d investigated their regulatory significance in different developmenta l and thyroid hormone states. The polyadenylation of alpha-MHC mRNA oc curs 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 m RNA) showed a significant increase in the proportion of the longest su bspecies and a decrease in the shortest subspecies. The second post-tr anscriptional event in alpha-MHC gene expression which was demonstrate d was the inclusion or exclusion of a codon, CAG, encoding glutamine a t position 1931, resulting from alternate splicing of the alpha-MHC tr anscript. The ratio of CAG+ and CAG- forms of mRNA in the adult euthyr oid hearts is 40:60% which was unchanged in hypo- and hyperthyroid sta tes. This is the first example of alternate splicing in a vertebrate s arcomeric myosin heavy chain gene. We conclude that the rat alpha-MHC gene transcript is post-transcriptionally modified.