title: NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly.
abstract: Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m(5)C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in conditional Nsun4 mouse knockouts. Deep sequencing of bisulfite-treated RNA shows that NSUN4 methylates cytosine 911 in 12S rRNA (m5C911) of the SSU. Surprisingly, NSUN4 does not need MTERF4 to generate this modification. Instead, the NSUN4/MTERF4 complex is required to assemble the SSU and LSU to form a monosome. NSUN4 is thus a dual function protein, which on the one hand is needed for 12S rRNA methylation and, on the other hand interacts with MTERF4 to facilitate monosome assembly. The presented data suggest that NSUN4 has a key role in controlling a final step in ribosome biogenesis to ensure that only the mature SSU and LSU are assembled.
authors: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors: Metodi Dimitrov
authors: MD
authors: Metodiev
authors: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors: Henrik
authors: H
authors: Spåhr
authors: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari, Italy.
authors: Paola
authors: P
authors: Loguercio Polosa
authors: Institute for Global Food Security, David Keir Building, Queen's University, Belfast, Northern Ireland.
authors: Caroline
authors: C
authors: Meharg
authors: Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors: Christian
authors: C
authors: Becker
authors: Cologne Center for Genomics, University of Cologne, Cologne, Germany.
authors: Janine
authors: J
authors: Altmueller
authors: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors: Bianca
authors: B
authors: Habermann
authors: Max Planck Institute for Biology of Ageing, Cologne, Germany ; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Nils-Göran
authors: NG
authors: Larsson
authors: Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors: Benedetta
authors: B
authors: Ruzzenente
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics* / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D014157:Transcription Factors; C495174:mTERF protein, mouse; D008780:Methyltransferases; C547055:SHTAP protein, mouse