Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation.
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 promoters. 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 3'UTRs of certain differentiation-specific RNAs are trans-acting regulators in a feedback loop that inhibits cell division and promotes differentiation.
Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
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D000199:Actins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000166:cytology*; D018008:Myogenin; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D014335:Tropomyosin / Q000235:genetics*; D014336:Troponin / Q000235:genetics*; D019210:Troponin I
D000199:Actins; D009124:Muscle Proteins; C503801:Myog protein, mouse; D018008:Myogenin; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014335:Tropomyosin; D014336:Troponin; D019210:Troponin I; D004247:DNA