CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins
| Autor: | David Pla-Martín, Henriette Hansen, Janine Altmueller, Elena I. Rugarli, Désirée Schatton, Jie Gao, Peter Frommolt, Esther Barth, Paola Martinelli, Marco Sardiello, Christian Becker |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Genetics
Messenger RNA RNA-Binding Proteins RNA Translation (biology) RNA-binding protein Cell Biology Biology Mitochondrion Mitochondria Cell biology Mitochondrial Proteins Mice Gene Expression Regulation Mitochondrial biogenesis Tubulin Protein Biosynthesis Report COS Cells Chlorocebus aethiops Protein biosynthesis Animals RNA Messenger Research Articles Biogenesis |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.201403129 |
| Popis: | CLUH is a cytosolic mRNA-binding protein that specifically binds a subset of mRNAs encoding mitochondrial proteins and may regulate their localized translation. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|