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

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 t...

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Autores principales: Gao, Jie, Schatton, Désirée, Martinelli, Paola, Hansen, Henriette, Pla-Martin, David, Barth, Esther, Becker, Christian, Altmueller, Janine, Frommolt, Peter, Sardiello, Marco, Rugarli, Elena I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210445/
https://www.ncbi.nlm.nih.gov/pubmed/25349259
http://dx.doi.org/10.1083/jcb.201403129
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author Gao, Jie
Schatton, Désirée
Martinelli, Paola
Hansen, Henriette
Pla-Martin, David
Barth, Esther
Becker, Christian
Altmueller, Janine
Frommolt, Peter
Sardiello, Marco
Rugarli, Elena I.
author_facet Gao, Jie
Schatton, Désirée
Martinelli, Paola
Hansen, Henriette
Pla-Martin, David
Barth, Esther
Becker, Christian
Altmueller, Janine
Frommolt, Peter
Sardiello, Marco
Rugarli, Elena I.
author_sort Gao, Jie
collection PubMed
description 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.
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spelling pubmed-42104452015-04-27 CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins Gao, Jie Schatton, Désirée Martinelli, Paola Hansen, Henriette Pla-Martin, David Barth, Esther Becker, Christian Altmueller, Janine Frommolt, Peter Sardiello, Marco Rugarli, Elena I. J Cell Biol Research Articles 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. The Rockefeller University Press 2014-10-27 /pmc/articles/PMC4210445/ /pubmed/25349259 http://dx.doi.org/10.1083/jcb.201403129 Text en © 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/).
spellingShingle Research Articles
Gao, Jie
Schatton, Désirée
Martinelli, Paola
Hansen, Henriette
Pla-Martin, David
Barth, Esther
Becker, Christian
Altmueller, Janine
Frommolt, Peter
Sardiello, Marco
Rugarli, Elena I.
CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title_full CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title_fullStr CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title_full_unstemmed CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title_short CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
title_sort cluh regulates mitochondrial biogenesis by binding mrnas of nuclear-encoded mitochondrial proteins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210445/
https://www.ncbi.nlm.nih.gov/pubmed/25349259
http://dx.doi.org/10.1083/jcb.201403129
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