期刊
Cell Research
标题
5-methylcytosine promotes mRNA export — NSUN2 as the methyltransferase and ALYREF as an m5C reader
作者
Xin Yang, Ying Yang, Bao-Fa Sun, Yu-Sheng Chen, Jia-Wei Xu, Wei-Yi Lai, Ang Li, Xing Wang, Devi Prasad Bhattarai, Wen Xiao, Hui-Ying Sun, Qin Zhu, Hai-Li Ma, Samir Adhikari, Min Sun, Ya-Juan Hao, Bing Zhang, Chun-Min Huang, Niu Huang, Gui-Bin Jiang, Yong-Liang Zhao, Hai-Lin Wang, Ying-Pu Sun & Yun-Gui Yang
摘要
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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