Rastinejad F, Blau H M
Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
Cell. 1993 Mar 26;72(6):903-17. doi: 10.1016/0092-8674(93)90579-f.
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.
分化的骨骼肌细胞停止分裂，并持续表达一系列组织特异性基因。为了鉴定生长和分化的调节因子，我们采用了基因互补方法。将cDNA表达文库导入分化缺陷型成肌细胞突变体（NMU2）后，分离出了激活肌肉特异性启动子的cDNA。互补的cDNA被鉴定为肌肉结构基因、肌钙蛋白I、原肌球蛋白和α-心肌肌动蛋白，它们的活性定位于3'非翻译区（3'UTR）。3'UTR增强了野生型肌肉细胞的分化。在10T1/2成纤维细胞中表达时，增殖受到抑制，这表明3'UTR的作用不限于成肌细胞。这些数据表明，某些分化特异性RNA的3'UTR是反馈回路中的反式作用调节因子，该反馈回路抑制细胞分裂并促进分化。
