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CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins

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Item Type:Article
Title:CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
Creators Name:Gao, J. and Schatton, D. and Martinelli, P. and Hansen, H. and Pla-Martin, D. and Barth, E. and Becker, C. and Altmueller, J. and Frommolt, P. and Sardiello, M. and Rugarli, E.I.
Abstract:Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)–binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.
Keywords:COS Cells, Chlorocebus Aethiops, Gene Expression Regulation, Messenger RNA, Mitochondria, Mitochondrial Proteins, Protein Biosynthesis, RNA-Binding Proteins, Tubulin, Animals, Mice
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press
Volume:207
Number:2
Page Range:213-223
Date:27 October 2014
Additional Information:Copyright © 2014 Gao et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Official Publication:https://doi.org/10.1083/jcb.201403129
PubMed:View item in PubMed

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