MicroRNA directly enhances mitochondrial translation during muscle differentiation.
MicroRNA directly enhances mitochondrial translation during muscle differentiation.
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DOI：
10.1016/j.cell.2014.05.047
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发表时间：
2014-07-31
期刊：
影响因子：
64.5
通讯作者：
Fu XD
中科院分区：
文献类型：
--
作者：
Zhang X;Zuo X;Yang B;Li Z;Xue Y;Zhou Y;Huang J;Zhao X;Zhou J;Yan Y;Zhang H;Guo P;Sun H;Guo L;Zhang Y;Fu XD
众所周知，microRNAs在细胞质中介导翻译抑制和mRNA降解。在膜分隔的细胞器中也检测到了各种microRNAs，但其功能意义仍不清楚。在这里，我们报告了miR-1，一种在肌肉发生过程中特异性诱导的微小RNA，有效地进入线粒体，在那里它出人意料地刺激而不是抑制特定线粒体基因组编码转录本的翻译。我们表明，这种积极的作用需要特定的miR：mRNA碱基配对和Ago2，但不需要它的功能伙伴GW182，后者被排除在线粒体之外。我们提供了Ago2通过CLIP-SEQ在线粒体翻译中的直接作用，线粒体靶向Ago2的功能挽救，以及选择性地抑制细胞质中的microRNA机制的证据。这些发现揭示了microRNA在线粒体翻译中的积极作用，并暗示了一种高度协调的生肌程序，即通过miR-1介导的线粒体翻译刺激和细胞质抑制。
MicroRNAs are well known to mediate translational repression and mRNA degradation in the cytoplasm. Various microRNAs have also been detected in membrane-compartmentalized organelles, but the functional significance has remained elusive. Here we report that miR-1, a microRNA specifically induced during myogenesis, efficiently enters the mitochondria where it unexpectedly stimulates, rather than represses, the translation of specific mitochondrial genome-encoded transcripts. We show that this positive effect requires specific miR:mRNA base-pairing and Ago2, but not its functional partner GW182, which is excluded from the mitochondria. We provide evidence for the direct action of Ago2 in mitochondrial translation by CLIP-seq, functional rescue with mitochondria-targeted Ago2, and selective inhibition of the microRNA machinery in the cytoplasm. These findings unveil a positive function of microRNA in mitochondrial translation and suggest a highly coordinated myogenic program via miR-1 mediated translational stimulation in the mitochondria and repression in the cytoplasm.
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