2. Academic Validation
  3. 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader

5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader

  • Cell Res. 2017 May;27(5):606-625. doi: 10.1038/cr.2017.55.
Xin Yang 1 2 3,  Ying Yang 2,  Bao-Fa Sun 2,  Yu-Sheng Chen 2 3,  Jia-Wei Xu 1 2,  Wei-Yi Lai 3 4,  Ang Li 2 3,  Xing Wang 2 5,  Devi Prasad Bhattarai 2 3,  Wen Xiao 2,  Hui-Ying Sun 2,  Qin Zhu 2 3,  Hai-Li Ma 2 3,  Samir Adhikari 2,  Min Sun 2,  Ya-Juan Hao 2,  Bing Zhang 2,  Chun-Min Huang 2,  Niu Huang 6,  Gui-Bin Jiang 4,  Yong-Liang Zhao 2,  Hai-Lin Wang 4,  Ying-Pu Sun 1,  Yun-Gui Yang 2 3
Affiliations

Affiliations

  • 1 Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.
  • 2 Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 School of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 5 Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 6 National Institute of Biological Sciences, Beijing 102206, China.
PMID: 28418038 DOI: 10.1038/cr.2017.55
Abstract

5-methylcytosine (m5C) is a post-transcriptional RNA modification identified in both stable and highly abundant tRNAs and rRNAs, and in mRNAs. However, its regulatory role in mRNA metabolism is still largely unknown. Here, we reveal that m5C modification is enriched in CG-rich regions and in regions immediately downstream of translation initiation sites and has conserved, tissue-specific and dynamic features across mammalian transcriptomes. Moreover, m5C formation in mRNAs is mainly catalyzed by the RNA methyltransferase NSUN2, and m5C is specifically recognized by the mRNA export adaptor ALYREF as shown by in vitro and in vivo studies. NSUN2 modulates ALYREF's nuclear-cytoplasmic shuttling, RNA-binding affinity and associated mRNA export. Dysregulation of ALYREF-mediated mRNA export upon NSUN2 depletion could be restored by reconstitution of wild-type but not methyltransferase-defective NSUN2. Our study provides comprehensive m5C profiles of mammalian transcriptomes and suggests an essential role for m5C modification in mRNA export and post-transcriptional regulation.

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