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来自武汉大学、加州大学圣地亚哥分校的研究人员证实,在肌肉分化过程中一种叫做miR-1的小RNA分子直接增强了线粒体基因的表达。这一重要的研究发现发表在7月31日的《细胞》(Cell)杂志上。

该项研究工作全部在武汉大学完成,生命科学学院博士生张晓荣为第一作者,通讯作者为长江学者讲座教授付向东(Xiang-Dong Fu)。其早年毕业于武汉大学病毒学系,是著名的美籍华人科学家,在分子生物学、生物化学等领域有较深造诣,在生命科学界付向东因发现SR家族的剪接因子和一个新的激酶家族而为众人瞩目。已在美国获得专利两项,在国际学术期刊发表论文100多篇,其中Nature 、Science、Cell论文十余篇。

MicroRNAs(miRNAs)是一类长度约为22个核苷酸的非编码单链RNA分子,它能与mRNA的特定位点结合,参与转录后基因表达调控,从而抑制蛋白质的合成。近年来大量的研究证实, miRNAs在调节基因转录与表达,调控生物体正常发育等各个生理过程中扮演重要角色,同时也对人类疾病的防治以及生物进化探索有着重要意义。

miRNAs的表达具有明显的组织特异性和发育阶段特异性。以往的研究已发现了一些在骨骼肌和心肌中特异表达的miRNAs。并证实miRNAs在肌肉的增殖、分化等发育过程中发挥重要的调节作用, miRNAs的表达异常与某些肌肉疾病的病理过程有关。

线粒体是一种存在于大多数真核细胞中的半自主细胞器。它是细胞内氧化磷酸化和合成三磷酸腺苷(ATP)的主要场所,为细胞的活动提供了能量,有“细胞动力工厂”之称。除了为细胞功能外,线粒体还参与诸如细胞分化、细胞信息传递和细胞凋亡等过程,并拥有调控细胞生长和细胞周期的能力。

在这篇文章中研究人员报告称,发现了一种在肌生长过程中特异性诱导表达的miRNA——miR-1。他们证实miR-1有效地进入到线粒体中,在那里它出乎意料地刺激了线粒体基因组编码的特异性转录物翻译。

研究人员证实,特异性的miR:mRNA碱基配对和Ago2是产生这一正效应的必要条件。他们通过交联免疫沉淀结合深度测序(crosslinking immunoprecipitation coupled with deep sequencing,CLIP-seq),利用线粒体靶向Ago2挽救功能,以及在细胞质中选择性抑制这一miRNA机器等方法,证实了Ago2对线粒体基因表达发挥直接作用。

这些研究结果证实了miR-1在线粒体基因表达中发挥正向功能,通过在线粒体中增强基因表达以及在细胞质中抑制基因表达,miR-1介导了一个高度协调的肌肉生成程序。由此本研究揭示了线粒体基因表达一种新调控方式,对肌肉细胞发育程序提供了新的阐释。

原文检索:
Xiaorong Zhang, Xinxin Zuo, Bo Yang, Zongran Li, Yuanchao Xue, Yu Zhou, Jie Huang, Xiaolu Zhao, Jie Zhou, Yun Yan, Huiqiong Zhang,Peipei Guo, Hui Sun, Lin Guo, Yi Zhang4, Xiang-Dong Fu. MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation. Cell, 31 July 2014; DOI: 
10.1016/j.cell.2014.05.047

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