NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly

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 translat...

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Bibliographic Details
Published in:PLoS genetics 2014-02, Vol.10 (2), p.e1004110-e1004110
Main Authors: Metodiev, Metodi Dimitrov, Spåhr, Henrik, Loguercio Polosa, Paola, Meharg, Caroline, Becker, Christian, Altmueller, Janine, Habermann, Bianca, Larsson, Nils-Göran, Ruzzenente, Benedetta
Format: Article
Language:English
Subjects:
Animals
Biology
Biosynthesis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cellular proteins
Crystal structure
DNA damage
DNA Methylation - genetics
Experiments
Genetic aspects
Genomes
Medicin och hälsovetenskap
Methyltransferases - genetics
Methyltransferases - metabolism
Mice
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Mitochondrial DNA
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Phosphorylation
Physiological aspects
Polypeptides
Protein Binding
Proteins
Ribosomal RNA
Ribosomes - genetics
Ribosomes - ultrastructure
RNA, Ribosomal - biosynthesis
RNA, Ribosomal - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1004110