β‐ and γ‐actin genes differ in their mechanisms of down‐regulation during myogenesis

During the differentiation of myoblasts to form myotubes, the expression patterns of the different actin isoforms change. The cytoplasmic actins, beta and gamma, are down-regulated and the muscle specific isoforms are up-regulated. The region responsible for the down-regulation of the beta-actin gene has been located in the 3'end of the gene. Since the beta- and gamma-actin genes arose from a gene duplication (Erba et al. [1988] J. Cell. Biol. 8:1775-1789), it is possible that the region responsible for down-regulation of the gamma-actin gene may also be in the 3'end of the gene. We have tested this by transfection of human gamma-actin gene constructs into myogenic C2 cells. To our surprise, we found that the region responsible for down-regulation of the gamma-actin gene during differentiation is not in the 3' end of the gene in contrast to that for beta-actin. Rather, we found that intron III is required for appropriate down-regulation of gamma-actin during myogenesis. Intron III containing transcripts from the gamma-actin gene were also found to accumulate during myogenesis. We, therefore, propose that excision of intron III from the primary transcript is inhibited during myogenesis resulting in degradation of the RNA. Removal of intron III from the gene allows it to escape this regulatory mechanism.