Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Jordan Hall 1232, Charlottesville, VA 22908, USA.
Mol Cell Biol. 2011 Jan;31(1):203-14. doi: 10.1128/MCB.01009-10. Epub 2010 Nov 1.
The Pax7 transcription factor is required for muscle satellite cell biogenesis and specification of the myogenic precursor lineage. Pax7 is expressed in proliferating myoblasts but is rapidly downregulated during differentiation. Here we report that miR-206 and -486 are induced during myoblast differentiation and downregulate Pax7 by directly targeting its 3' untranslated region (UTR). Expression of either of these microRNAs in myoblasts accelerates differentiation, whereas inhibition of these microRNAs causes persistence of Pax7 protein and delays differentiation. A microRNA-resistant form of Pax7 is sufficient to inhibit differentiation. Since both these microRNAs are induced by MyoD and since Pax7 promotes the expression of Id2, an inhibitor of MyoD, our results revealed a bistable switch that exists either in a Pax7-driven myoblast state or a MyoD-driven myotube state.
Pax7 转录因子对于肌肉卫星细胞的发生和生肌前体细胞谱系的特化是必需的。Pax7 在增殖的成肌细胞中表达,但在分化过程中迅速下调。在这里,我们报告说,miR-206 和 miR-486 在成肌细胞分化过程中被诱导,并通过直接靶向其 3'非翻译区 (UTR) 下调 Pax7。这些 microRNAs 中的任何一种在成肌细胞中的表达都加速了分化,而抑制这些 microRNAs 会导致 Pax7 蛋白的持续存在并延迟分化。Pax7 的 microRNA 抗性形式足以抑制分化。由于这两种 microRNAs 都是由 MyoD 诱导的,并且 Pax7 促进了 MyoD 抑制剂 Id2 的表达,我们的结果揭示了一种双稳态开关,它存在于 Pax7 驱动的成肌细胞状态或 MyoD 驱动的肌管状态中。