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  NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly

Metodiev, M. D., Spåhr, H., Polosa, P. L., Meharg, C., Becker, C., Altmueller, J., et al. (2014). NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly. PLOS GENETICS, 10(2): e1004110. doi:10.1371/journal.pgen.1004110.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-D278-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-7B27-C
Genre: Journal Article

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 Creators:
Metodiev, Metodi D.1, Author              
Spåhr, Henrik2, Author              
Polosa, Paola Loguercio3, Author
Meharg, Caroline3, Author
Becker, Christian3, Author
Altmueller, Janine3, Author
Habermann, Bianca H.4, Author              
Larsson, Nils-Göran2, Author              
Ruzzenente, Benedetta2, Author              
Affiliations:
1Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942294              
2Mitochondrial Biology, Department Larsson, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942293              
3external, ou_persistent22              
4Bioinformatics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942302              

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 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.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
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Title: PLOS GENETICS
Source Genre: Journal
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Pages: - Volume / Issue: 10 (2) Sequence Number: e1004110 Start / End Page: - Identifier: ISSN: 1553-7404