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MTERF4 Regulates Translation by Targeting the Methyltransferase NSUN4 to the Mammalian Mitochondrial Ribosome
Yolanda Camara, 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, and Nils-Goran Larsson
SummaryPrecise 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.