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

By Xin Yang, Ying Yang, Bao-Fa Sun, Yu-Sheng Chen, Jiawei Xu, Weiyi Lai, Ang Li, Xing Wang, Devi Prasad Bhattarai, Wen Xiao and 14 more. Cell Research, 2017

958 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/07dab57679e6d3558f6034760b6cc0e840b459b0

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In Molecular Biology

1. Li Shen
2. Xiaofeng Dai

Citations in the corpus

• Methylation multiplicity and its clinical values in cancer (2021, neutral): “27).”
• Advances and Trends in Omics Technology Development (2022, background): “For instance, RNA bisulfite sequencing (RNA-BisSeq) is one of these approaches that relies on chemical deamination of cytidine to uridine by sodium bisulfite, leaving m5C intact (151–153).”