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 journalArticle

76 Scopus citations

Abstract

N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury. Loss of either m6A methyltransferase complex component Mettl14 or m6A-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.

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

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    Weng, Y-L., Wang, X., An, R., Cassin, J., Vissers, C., Liu, Y., Liu, Y., Xu, T., Wang, X., Wong, S. Z. H., Joseph, J., Dore, L. C., Dong, Q., Zheng, W., Jin, P., Wu, H., Shen, B., Zhuang, X., He, C., ... Ming, G-L. (2018). Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian Nervous System. Neuron, 97(2), 313-325.e6. https://doi.org/10.1016/j.neuron.2017.12.036