Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA; Department of Molecular and Cellular Biology and the Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Cellular Biology and the Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Cell Rep. 2018 Aug 14;24(7):1852-1864. doi: 10.1016/j.celrep.2018.07.046.
RNA polymerase (pol) III transcribes a variety of small untranslated RNAs involved in transcription, RNA processing, and translation. RNA pol III and its components are altered in various human developmental disorders, yet their roles in cell fate determination and development are poorly understood. Here we demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation. RNA pol III repression by chemical inhibition or knockdown of Brf1 promotes adipogenesis. Altered RNA pol III-dependent transcription produces select changes in mRNAs with a significant enrichment of adipogenic gene signatures. Furthermore, RNA pol III-mediated transcription positively regulates long non-coding RNA H19 and Wnt6 expression, established adipogenesis inhibitors. Together, these studies reveal an important and unexpected function for RNA pol III-mediated transcription and Maf1 in mesoderm induction and adipocyte differentiation.
RNA 聚合酶（pol）III 转录多种参与转录、RNA 加工和翻译的小非翻译 RNA。RNA pol III 及其成分在各种人类发育障碍中发生改变，但它们在细胞命运决定和发育中的作用知之甚少。在这里，我们证明转录抑制剂 Maf1 可促进小鼠胚胎干细胞（mESC）向中胚层的诱导。mESC 和前脂肪细胞中 Maf1 表达减少会损害脂肪生成，而在 Maf1 缺陷细胞中外源表达 Maf1 则增强分化。化学抑制或 Brf1 敲低抑制 RNA pol III 可促进脂肪生成。改变 RNA pol III 依赖性转录会产生 mRNA 的选择性变化，其中脂肪生成基因特征显著富集。此外，RNA pol III 介导的转录正向调节长非编码 RNA H19 和 Wnt6 的表达，这两种物质是已知的脂肪生成抑制剂。总之，这些研究揭示了 RNA pol III 介导的转录和 Maf1 在中胚层诱导和脂肪细胞分化中的重要且意外的功能。
