Volume 27, No 5, May 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 5, May 2017: 606-625 | Open Access
ORIGINAL ARTICLES
5-methylcytosine promotes mRNA export — NSUN2 as the methyltransferase and ALYREF as an m5C reader
Xin Yang1,2,3,*, Ying Yang2,*, Bao-Fa Sun2,*, Yu-Sheng Chen2,3,*, Jia-Wei Xu1,2,*, Wei-Yi Lai3,4,*, Ang Li2,3, Xing Wang2,5, Devi Prasad Bhattarai2,3, Wen Xiao2, Hui-Ying Sun2, Qin Zhu2,3, Hai-Li Ma2,3, Samir Adhikari2, Min Sun2, Ya-Juan Hao2, Bing Zhang2, Chun-Min Huang2, Niu Huang6, Gui-Bin Jiang4, Yong-Liang Zhao2, Hai-Lin Wang4, Ying-Pu Sun1 and Yun-Gui Yang2,3
1Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China
2Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
3School of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China
4State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
5Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China
6National Institute of Biological Sciences, Beijing 102206, China
Correspondence: Yun-Gui Yang, Tel: +86-10-84097642 E-mail: ygyang@big.ac.cn; Ying-Pu Sun, E-mail: syp2008@vip.sina.com; Hai-Lin Wang,(hlwang@rcees.ac.cn)
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.
10.1038/cr.2017.55
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