Cell
Volume 158, Issue 3, 31 July 2014, Pages 607-619
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Article
MicroRNA Directly Enhances Mitochondrial Translation during Muscle Differentiation

https://doi.org/10.1016/j.cell.2014.05.047Get rights and content
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Highlights

  • miR-1, Argonaute 2, but not GW182, are localized in the mitochondria

  • Argonaute 2 binds mitochondrial transcripts and ribosomal RNAs

  • microRNAs are able to directly enhance mitochondrial translation

  • miR-1 mediates a coordinated myogenic program for muscle differentiation

Summary

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 crosslinking immunoprecipitation coupled with deep sequencing (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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Present address: Center for Genome Analysis, ABLife Inc., Novonest Building 135, 8 Nanhu Avenue, East Lake Hi-Tech Development Zone, Wuhan, Hubei 430079, China