Universität zu Köln

Lagouge, Marie, Mourier, Arnaud, Lee, Hyun Ju, Spahr, Henrik, Wai, Timothy ORCID: 0000-0002-6770-6222, Kukat, Christian ORCID: 0000-0003-1508-0229, Ramos, Eduardo Silva, Motori, Elisa, Busch, Jakob D., Siira, Stefan ORCID: 0000-0002-8391-0143, Kremmer, Elisabeth, Filipovska, Aleksandra ORCID: 0000-0002-6998-8403 and Larsson, Nils-Goeran (2015). SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation. PLoS Genet., 11 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lagouge, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Mourier, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Hyun Ju UNSPECIFIED UNSPECIFIED UNSPECIFIED Spahr, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Kukat, Christian UNSPECIFIED orcid.org/0000-0003-1508-0229 UNSPECIFIED Ramos, Eduardo Silva UNSPECIFIED UNSPECIFIED UNSPECIFIED Motori, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Jakob D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siira, Stefan UNSPECIFIED orcid.org/0000-0002-8391-0143 UNSPECIFIED Kremmer, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Filipovska, Aleksandra UNSPECIFIED orcid.org/0000-0002-6998-8403 UNSPECIFIED Larsson, Nils-Goeran UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-398290
DOI:	10.1371/journal.pgen.1005423
Journal or Publication Title:	PLoS Genet.
Volume:	11
Number:	8
Date:	2015
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNAS; POLYNUCLEOTIDE PHOSPHORYLASE; MAMMALIAN MITOCHONDRIA; LON PROTEASE; TRANSLATION; POLYADENYLATION; BINDING; IDENTIFICATION; TRANSCRIPTION; COORDINATION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39829