例如:"lncRNA", "apoptosis", "WRKY"

NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs.

Nucleic Acids Res. 2019 Sep 19;47(16):8720-8733
Lindsey Van Haute 1 , Song-Yi Lee 2 , Beverly J McCann 1 , Christopher A Powell 1 , Dhiru Bansal 3 , Lina Vasiliauskaitė 4 , Caterina Garone 1 , Sanghee Shin 5 , Jong-Seo Kim 5 , Michaela Frye 6 , Joseph G Gleeson 7 , Eric A Miska 8 , Hyun-Woo Rhee 2 , Michal Minczuk 1
Lindsey Van Haute 1 , Song-Yi Lee 2 , Beverly J McCann 1 , Christopher A Powell 1 , Dhiru Bansal 3 , Lina Vasiliauskaitė 4 , Caterina Garone 1 , Sanghee Shin 5 , Jong-Seo Kim 5 , Michaela Frye 6 , Joseph G Gleeson 7 , Eric A Miska 8 , Hyun-Woo Rhee 2 , Michal Minczuk 1
+ et al

[No authors listed]

Author information
  • 1 Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
  • 2 Department of Chemistry, Seoul National University, Gwanak-ro 1, Seoul 08826, South Korea.
  • 3 Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
  • 4 STORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 5 School of Biological Sciences, Seoul National University, Seoul 08826, Korea.
  • 6 German Cancer Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • 7 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
  • 8 Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.

摘要


Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been detected in mitochondrial transcriptome, however its biogenesis has not been investigated in details. Mammalian NOP2/Sun RNA Methyltransferase Family Member 2 (NSUN2) has been characterized as an RNA methyltransferase introducing m5C in nuclear-encoded tRNAs, mRNAs and microRNAs and associated with cell proliferation and differentiation, with pathogenic variants in NSUN2 being linked to neurodevelopmental disorders. Here we employ spatially restricted proximity labelling and immunodetection to demonstrate that NSUN2 is imported into the matrix of mammalian mitochondria. Using three genetic models for NSUN2 inactivation-knockout mice, patient-derived fibroblasts and CRISPR/Cas9 knockout in human cells-we show that NSUN2 is necessary for the generation of m5C at positions 48, 49 and 50 of several mammalian mitochondrial tRNAs. Finally, we show that inactivation of NSUN2 does not have a profound effect on mitochondrial tRNA stability and oxidative phosphorylation in differentiated cells. We discuss the importance of the newly discovered function of NSUN2 in the context of human disease.