Cargando…
SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation
We have studied the in vivo role of SLIRP in regulation of mitochondrial DNA (mtDNA) gene expression and show here that it stabilizes its interacting partner protein LRPPRC by protecting it from degradation. Although SLIRP is completely dependent on LRPPRC for its stability, reduced levels of LRPPRC...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527767/ https://www.ncbi.nlm.nih.gov/pubmed/26247782 http://dx.doi.org/10.1371/journal.pgen.1005423 |
_version_ | 1782384613213077504 |
---|---|
author | Lagouge, Marie Mourier, Arnaud Lee, Hyun Ju Spåhr, Henrik Wai, Timothy Kukat, Christian Silva Ramos, Eduardo Motori, Elisa Busch, Jakob D. Siira, Stefan Kremmer, Elisabeth Filipovska, Aleksandra Larsson, Nils-Göran |
author_facet | Lagouge, Marie Mourier, Arnaud Lee, Hyun Ju Spåhr, Henrik Wai, Timothy Kukat, Christian Silva Ramos, Eduardo Motori, Elisa Busch, Jakob D. Siira, Stefan Kremmer, Elisabeth Filipovska, Aleksandra Larsson, Nils-Göran |
author_sort | Lagouge, Marie |
collection | PubMed |
description | We have studied the in vivo role of SLIRP in regulation of mitochondrial DNA (mtDNA) gene expression and show here that it stabilizes its interacting partner protein LRPPRC by protecting it from degradation. Although SLIRP is completely dependent on LRPPRC for its stability, reduced levels of LRPPRC persist in the absence of SLIRP in vivo. Surprisingly, Slirp knockout mice are apparently healthy and only display a minor weight loss, despite a 50–70% reduction in the steady-state levels of mtDNA-encoded mRNAs. In contrast to LRPPRC, SLIRP is dispensable for polyadenylation of mtDNA-encoded mRNAs. Instead, deep RNA sequencing (RNAseq) of mitochondrial ribosomal fractions and additional molecular analyses show that SLIRP is required for proper association of mRNAs to the mitochondrial ribosome and efficient translation. Our findings thus establish distinct functions for SLIRP and LRPPRC within the LRPPRC-SLIRP complex, with a novel role for SLIRP in mitochondrial translation. Very surprisingly, our results also demonstrate that mammalian mitochondria have a great excess of transcripts under basal physiological conditions in vivo. |
format | Online Article Text |
id | pubmed-4527767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45277672015-08-12 SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation Lagouge, Marie Mourier, Arnaud Lee, Hyun Ju Spåhr, Henrik Wai, Timothy Kukat, Christian Silva Ramos, Eduardo Motori, Elisa Busch, Jakob D. Siira, Stefan Kremmer, Elisabeth Filipovska, Aleksandra Larsson, Nils-Göran PLoS Genet Research Article We have studied the in vivo role of SLIRP in regulation of mitochondrial DNA (mtDNA) gene expression and show here that it stabilizes its interacting partner protein LRPPRC by protecting it from degradation. Although SLIRP is completely dependent on LRPPRC for its stability, reduced levels of LRPPRC persist in the absence of SLIRP in vivo. Surprisingly, Slirp knockout mice are apparently healthy and only display a minor weight loss, despite a 50–70% reduction in the steady-state levels of mtDNA-encoded mRNAs. In contrast to LRPPRC, SLIRP is dispensable for polyadenylation of mtDNA-encoded mRNAs. Instead, deep RNA sequencing (RNAseq) of mitochondrial ribosomal fractions and additional molecular analyses show that SLIRP is required for proper association of mRNAs to the mitochondrial ribosome and efficient translation. Our findings thus establish distinct functions for SLIRP and LRPPRC within the LRPPRC-SLIRP complex, with a novel role for SLIRP in mitochondrial translation. Very surprisingly, our results also demonstrate that mammalian mitochondria have a great excess of transcripts under basal physiological conditions in vivo. Public Library of Science 2015-08-06 /pmc/articles/PMC4527767/ /pubmed/26247782 http://dx.doi.org/10.1371/journal.pgen.1005423 Text en © 2015 Lagouge et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lagouge, Marie Mourier, Arnaud Lee, Hyun Ju Spåhr, Henrik Wai, Timothy Kukat, Christian Silva Ramos, Eduardo Motori, Elisa Busch, Jakob D. Siira, Stefan Kremmer, Elisabeth Filipovska, Aleksandra Larsson, Nils-Göran SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title | SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title_full | SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title_fullStr | SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title_full_unstemmed | SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title_short | SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation |
title_sort | slirp regulates the rate of mitochondrial protein synthesis and protects lrpprc from degradation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527767/ https://www.ncbi.nlm.nih.gov/pubmed/26247782 http://dx.doi.org/10.1371/journal.pgen.1005423 |
work_keys_str_mv | AT lagougemarie slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT mourierarnaud slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT leehyunju slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT spahrhenrik slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT waitimothy slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT kukatchristian slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT silvaramoseduardo slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT motorielisa slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT buschjakobd slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT siirastefan slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT kremmerelisabeth slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT filipovskaaleksandra slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation AT larssonnilsgoran slirpregulatestherateofmitochondrialproteinsynthesisandprotectslrpprcfromdegradation |