title: MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome.
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.
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Cámara
authors.forename: Jorge
authors.initials: J
authors.lastname: Asin-Cayuela
authors.forename: Chan Bae
authors.initials: CB
authors.lastname: Park
authors.forename: Metodi D
authors.initials: MD
authors.lastname: Metodiev
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Ruzzenente
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: B Martin
authors.initials: BM
authors.lastname: Hallberg
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D009202:Cardiomyopathies; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D019426:Integrases / Q000378:metabolism; D008780:Methyltransferases; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics*; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis; D011496:Protein Methyltransferases / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics; D012269:Ribosomal Proteins / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; C000619858:MTERF4 protein, mouse; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D014157:Transcription Factors; D008780:Methyltransferases; D011496:Protein Methyltransferases; C547055:SHTAP protein, mouse; C045073:Cre recombinase; D019426:Integrases