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Lagouge, M.* ; Mourier, A.* ; Lee, H.J.* ; Spåhr, H.* ; Wai, T.* ; Kukat, C.* ; Silva Ramos, E.* ; Motori, E.* ; Busch, J.D.* ; Siira, S.* ; German Mouse Clinic Consortium (Larsson, N.G.* ; Aguilar-Pimentel, J.A. ; Amarie, O.V. ; Becker, L. ; Beckers, J. ; Brachthäuser, L. ; Calzada-Wack, J. ; Eickelberg, O. ; Gailus-Durner, V. ; Garrett, L. ; Graw, J. ; Hans, W. ; Hölter, S.M. ; Horsch, M. ; Hrabě de Angelis, M. ; Janik, D. ; Klein-Rodewald, T. ; Lengger, C. ; Leuchtenberger, S. ; Maier, H. ; Moreth, K. ; Neff, F. ; Östereicher, M.A. ; Puk, O. ; Rácz, I. ; Rathkolb, B. ; Rozman, J. ; Steinkamp, R. ; Stoeger, C. ; Stöger, T. ; Vernaleken, A. ; Wurst, W. ; Yildirim, A.Ö. ; Zimprich, A.) ; Kremmer, E. ; Filipovska, A.*

SLIRP regulates the rate of mitochondrial protein synthesis and protects LRPPRC from degradation.

PLoS Genet. 11:e1005423 (2015)
Publ. Version/Full Text DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 11, Issue: 8, Pages: , Article Number: e1005423 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Institute of Pathology (PATH)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30201 - Metabolic Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Genetics and Epidemiology
Enabling and Novel Technologies
Immune Response and Infection
PSP Element(s) G-500600-001
G-500600-002
G-500600-004
G-500692-001
G-500500-001
G-500500-002
G-500300-001
G-501793-001
PubMed ID 26247782
DOI 10.1371/journal.pgen.1005423
WOS ID WOS:000360823100019
Erfassungsdatum 2015-08-09
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