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

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…

• AO
  Academy of Medical Sciences
• NN
  National Natural Science Foundation of China

  Awards: 31670824, 31625016
• CA
  Chinese Academy of Sciences
• MO
  Ministry of Science and Technology of the People's Republic of China
• ZU
  Zhengzhou University
• CA
  Chinese Academy of Medical Sciences
• FA
  First Affiliated Hospital of Zhengzhou University