Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian Nervous System

Yi-Lan Weng, Xu Wang, Ran An, Jessica Cassin, Caroline Vissers, Yuanyuan Liu, Yajing Liu, Tianlei Xu, Xinyuan Wang, Samuel Zheng Hao Wong, Jessica Joseph, Louis C Dore, Qiang Dong, Wei Zheng, Peng Jin, Hao Wu, Bin Shen, Xiaoxi Zhuang, Chuan He, Kai LiuHongjun Song, Guo-Li Ming

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

N 6-methyladenosine (m 6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m 6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m 6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m 6A-CLIP mapping further reveals a dynamic m 6A landscape in the adult DRG upon injury. Loss of either m 6A methyltransferase complex component Mettl14 or m 6A-binding protein Ythdf1 globally attenuates injury-induced protein translation in adult DRGs and reduces functional axon regeneration in the peripheral nervous system in vivo. Furthermore, Pten deletion-induced axon regeneration of retinal ganglion neurons in the adult central nervous system is attenuated upon Mettl14 knockdown. Our study reveals a critical epitranscriptomic mechanism in promoting injury-induced protein synthesis and axon regeneration in the adult mammalian nervous system. N 6-methyladenosine (m 6A) occurs in many mRNAs. Weng et al. uncovered an epitranscriptomic mechanism wherein axonal injury elevates m 6A levels and signaling to promote protein translation, including regeneration-associated genes, which is essential for functional axon regeneration of peripheral sensory neurons.

Original languageEnglish (US)
Pages (from-to)313-325.e6
JournalNeuron
Volume97
Issue number2
DOIs
StatePublished - Jan 17 2018

Keywords

  • CNS axon regeneration
  • DRG
  • Mettl14
  • PNS axon regeneration
  • RGC
  • YTHDF1
  • epitranscriptomics
  • mRNA methylation
  • protein synthesis

ASJC Scopus subject areas

  • Neuroscience(all)

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