title: SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation.
abstract: 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.
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Lagouge
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Spåhr
authors.affiliation: CECAD Research Center, University of Cologne, Cologne, Germany.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wai
authors.affiliation: FACS and Imaging facility, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Silva Ramos
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Motori
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Jakob D
authors.initials: JD
authors.lastname: Busch
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research and School of Chemistry and Biochemistry, The University of Western Australia, Perth, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Siira
authors.affiliation: Helmholtz Zentrum München, Institute of Molecular Immunology, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research and School of Chemistry and Biochemistry, The University of Western Australia, Perth, Australia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Filipovska
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000378:metabolism*; D026723:Polyadenylation; D014176:Protein Biosynthesis; D059748:Proteolysis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism
chemical_list: C486222:Lrpprc protein, mouse; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C544451:SLIRP protein, mouse