DIRECT RELATIONSHIP BETWEEN THE EXPRESSION OF TUMOR-SUPPRESSOR H19 MESSENGER-RNA AND C-MOS PROTOONCOGENE DURING MYOGENESIS

We have cloned and sequenced an almost complete c-DNA and the entire g enomic sequence of rat the H19 gene, which is developmentally regulate d in skeletal muscle, The data base comparison revealed a 92% homology with mouse gene H19. However the rat H19 ORFs do not display signific ant homology with the H19 ORFs from other species, In contrast to the mouse, the rat H19 mRNA is not easily detectable in fetal rat skeletal fibers. Its level increases after birth (up to 12 to 18 days) and rem ains stable thereafter. The pattern of H19 mRNA expression in rat musc le in vivo is very similar to the c-mos gene expression in this tissue , suggesting an interrelationship between H19 and c-mos products durin g muscle differentiation. Indeed, our results indicate that overexpres sion of c-mos protein in the muscle cell line C2C12 induces a concomit ant increase of H19 mRNA expression. Furthermore, repression of c-mos protein expression by anti-sense RNAs extinguishes H19 mRNA expression and inhibits the differentiation process. These data suggest a relati onship between c-mos and H19 expression and, in addition, the involvem ent of both gene products in the process of myogenesis.