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

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons129971

Metodiev,  Metodi D.
Biological Mechanisms of Ageing, Department Partridge, Max Planck Institute for Biology of Ageing, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons129418

Spåhr,  Henrik
Mitochondrial Biology, Department Larsson, Max Planck Institute for Biology of Ageing, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons129853

Habermann,  Bianca H.
Bioinformatics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons129342

Larsson,  Nils-Göran
Mitochondrial Biology, Department Larsson, Max Planck Institute for Biology of Ageing, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons129416

Ruzzenente,  Benedetta
Mitochondrial Biology, Department Larsson, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Zitation

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.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0019-D278-5
Zusammenfassung
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.