Rastinejad F, and Blau HM, Department of Molecular Pharmacology, School of Medicine, Stanford University,
Stanford, CA 94305-5332 USA.

Differentiated skeletal muscle cells cease dividing and sustain expression of a battery of tissue-specific genes. To identify regulators of growth and differentiation, we used a genetic complementation approach. Following introduction of a cDNA expression library into a differentiation-defective myoblast mutant (NMU2), cDNAs were isolated that activated muscle-specific promotors. The complementing cDNAs were identified as muscle structural genes, troponin I, tropomyosin, and alpha-cardiac actin, and their activity was mapped to the 3' untranslated region (3'UTR). The 3'UTRs augmented the differentiation of wild-type muscle cells. Upon expression in 10T1/2 fibroblasts, proliferation was suppressed, indicating that the effects of the 3'UTRs are not limited to myogenic cells. These data suggest that the 3'UTRs of certain differentiation-specific RNAs are trans-acting regulators in a feedback loop that inhibits cell division and promotes differentiation.

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