MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome

Yolanda Cámara; Jorge Asin-Cayuela; Chan Bae Park; Metodi D Metodiev; Yonghong Shi; Benedetta Ruzzenente; Christian Kukat; Bianca Habermann; Rolf Wibom; Kjell Hultenby; Thomas Franz; Hediye Erdjument-Bromage; Paul Tempst; B Martin Hallberg; Claes M Gustafsson; Nils-Göran Larsson

doi:10.1016/j.cmet.2011.04.002

MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome

Cell Metab. 2011 May 4;13(5):527-39. doi: 10.1016/j.cmet.2011.04.002.

Authors

Yolanda Cámara¹, Jorge Asin-Cayuela, Chan Bae Park, Metodi D Metodiev, Yonghong Shi, Benedetta Ruzzenente, Christian Kukat, Bianca Habermann, Rolf Wibom, Kjell Hultenby, Thomas Franz, Hediye Erdjument-Bromage, Paul Tempst, B Martin Hallberg, Claes M Gustafsson, Nils-Göran Larsson

Affiliation

¹ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

PMID: 21531335
DOI: 10.1016/j.cmet.2011.04.002

Abstract

Precise control of mitochondrial DNA gene expression is critical for regulation of oxidative phosphorylation capacity in mammals. The MTERF protein family plays a key role in this process, and its members have been implicated in regulation of transcription initiation and site-specific transcription termination. We now demonstrate that a member of this family, MTERF4, directly controls mitochondrial ribosomal biogenesis and translation. MTERF4 forms a stoichiometric complex with the ribosomal RNA methyltransferase NSUN4 and is necessary for recruitment of this factor to the large ribosomal subunit. Loss of MTERF4 leads to defective ribosomal assembly and a drastic reduction in translation. Our results thus show that MTERF4 is an important regulator of translation in mammalian mitochondria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Northern
Cardiomyopathies
Carrier Proteins / genetics
Carrier Proteins / metabolism*
DNA, Mitochondrial / genetics
Gene Expression Regulation, Developmental*
Immunoprecipitation
Integrases / metabolism
Methyltransferases
Mice
Mice, Knockout
Mitochondria / genetics*
Mitochondria / metabolism*
Mitochondrial Diseases / genetics
Mitochondrial Diseases / pathology
Mitochondrial Proteins / genetics*
Oxidative Phosphorylation
Protein Biosynthesis*
Protein Methyltransferases / metabolism*
RNA, Ribosomal / genetics
Ribosomal Proteins / physiology*
Ribosomes / metabolism*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Transcription Factors / genetics*
Transcription, Genetic

Substances

Carrier Proteins
DNA, Mitochondrial
MTERF4 protein, mouse
Mitochondrial Proteins
RNA, Ribosomal
Ribosomal Proteins
Transcription Factors
Methyltransferases
Protein Methyltransferases
SHTAP protein, mouse
Cre recombinase
Integrases