title: MicroRNA directly enhances mitochondrial translation during muscle differentiation.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Zongran
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Huiqiong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA. Electronic address: xdfu@ucsd.edu.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse
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