Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs

Saori Shinoda, Sho Kitagawa, Shinichi Nakagawa, Fan Yan Wei, Kazuhito Tomizawa, Kimi Araki, Masatake Araki, Takeo Suzuki, Tsutomu Suzuki

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Post-transcriptional modifications in mitochondrial tRNAs (mt-tRNAs) play critical roles in mitochondrial protein synthesis, which produces respiratory chain complexes. In this study, we took advantage of mass spectrometric analysis to map 5- methylcytidine (m5C) at positions 48-50 in eight mouse and six human mt-tRNAs. We also confirmed the absence ofm5C inmt-tRNAs isolated fromNsun2 knockout (KO) mice, as well as from NSUN2 KO human culture cells. In addition, we successfully reconstituted m5C at positions 48-50 of mt-tRNA in vitro with NSUN2 protein in the presence of Sadenosylmethionine. Although NSUN2 is predominantly localized to the nucleus and introduces m5C into cytoplasmic tRNAs and mRNAs, structured illumination microscopy clearly revealed NSUN2 foci inside mitochondria. These observations provide novel insights into the role of NSUN2 in the physiology and pathology of mitochondrial functions.

Original languageEnglish
Pages (from-to)8734-8745
Number of pages12
JournalNucleic Acids Research
Issue number16
Publication statusPublished - 2019 Sept 19


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