Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative (CBI), Université de Toulouse, UPS, CNRS, France.
PLoS Genet. 2018 Mar 8;14(3):e1007226. doi: 10.1371/journal.pgen.1007226. eCollection 2018 Mar.
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles.
在组织特异性背景下,基因表达取决于表观遗传、转录和转录后等多种过程的共同作用,这些过程最终导致产生特定的蛋白质,而这些蛋白质是细胞身份的重要决定因素。核糖体是细胞中蛋白质生物合成机制的核心组成部分;然而,其在骨骼肌肉基因表达的翻译调控中的调节作用仍有待确定。在一项旨在鉴定成肌分化关键调控因子的基因筛选中,我们鉴定到一个 DEAD-Box RNA 解旋酶 DDX27,它是骨骼肌肉生长和再生所必需的。我们证明 DDX27 调节核糖体 RNA(rRNA) 的成熟,从而调节核糖体生物发生以及在成肌分化过程中特定转录本的翻译。这些发现为成肌分化中基因表达的翻译调控提供了新的见解,并提示核糖体在调节骨骼肌肉中基因表达方面具有新的功能。