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129 TRANSCRIPT-SWITCHING IS THE BASIS FOR CHANGE IN AMP DEMINASE ISOFORMS DURING IN VIVO AND IN VITRO MYOCYTE DIFFERENTIATION

It is well established that many muscle-specific genes undergo switching of non-muscle to muscle isoforms during myogenesis, accompanied by a switch in RNA transcripts. Previously we had reported developmental isoforms of AMP deaminase (AMP–D) in skeletal muscle (Marquetant et al, PNAS 84: 2345, 1987). Subsequent cloning of the rat AMP-D cDNA (Sabina et al, JBC 262: 12397, 1987) has also enabled the analysis of transcript expression during myogenesis. The results of these experiments are as follows: 1) In the early embryo in situ or in proliferating myoblasts in culture, a 3.4 Kb transcript is expressed which encodes the embryonic AMP-D peptide. 2) The amount of this transcript increases during neonatal development in situ and during the transition to myotubes in culture. Concurrently, a 2.5 Kb adult muscle transcript begins to appear. During this time, however, all AMP-D activity is immunoprecipitated by antiserum specific for the embryonic isoform 3) late in neonatal development and in fully differentiated myotubes in culture, the embryonic transcript and the embryonic peptide disappear. During this interval there is an increase in the abundance of the adult muscle transcript and the adult muscle peptide appears. These results establish transcript switching as the basis for the change in AMP-D isoforms during myogenesis. These results also demonstrate that the AMP-D gene is controlled through transcriptional regulation presumably in response to tissue-specific factors. Additionally it appears that the adult muscle AMP-D transcript is subject to post-transcriptional regulation as well.