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...
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2015-08-01
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doaj-e1bf9ab72edd4e89b4da90f9911339062020-11-24T22:01:12ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-08-01118e100542310.1371/journal.pgen.1005423SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation.Marie LagougeArnaud MourierHyun Ju LeeHenrik SpåhrTimothy WaiChristian KukatEduardo Silva RamosElisa MotoriJakob D BuschStefan SiiraGerman Mouse Clinic ConsortiumElisabeth KremmerAleksandra FilipovskaNils-Göran LarssonWe 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.http://europepmc.org/articles/PMC4527767?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marie Lagouge Arnaud Mourier Hyun Ju Lee Henrik Spåhr Timothy Wai Christian Kukat Eduardo Silva Ramos Elisa Motori Jakob D Busch Stefan Siira German Mouse Clinic Consortium Elisabeth Kremmer Aleksandra Filipovska Nils-Göran Larsson |
spellingShingle |
Marie Lagouge Arnaud Mourier Hyun Ju Lee Henrik Spåhr Timothy Wai Christian Kukat Eduardo Silva Ramos Elisa Motori Jakob D Busch Stefan Siira German Mouse Clinic Consortium Elisabeth Kremmer Aleksandra Filipovska Nils-Göran Larsson SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation. PLoS Genetics |
author_facet |
Marie Lagouge Arnaud Mourier Hyun Ju Lee Henrik Spåhr Timothy Wai Christian Kukat Eduardo Silva Ramos Elisa Motori Jakob D Busch Stefan Siira German Mouse Clinic Consortium Elisabeth Kremmer Aleksandra Filipovska Nils-Göran Larsson |
author_sort |
Marie Lagouge |
title |
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_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_sort |
slirp regulates the rate of mitochondrial protein synthesis and protects lrpprc from degradation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2015-08-01 |
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. |
url |
http://europepmc.org/articles/PMC4527767?pdf=render |
work_keys_str_mv |
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