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

被引：347

作者：

Weng, Yi-Lan ^{[1
,2
]}

Wang, Xu ^{[3
]}

An, Ran ^{[1
,2
,4
]}

Cassin, Jessica ^{[5
]}

Vissers, Caroline ^{[6
]}

Liu, Yuanyuan ^{[7
]}

Liu, Yajing ^{[8
]}

Xu, Tianlei ^{[9
]}

Wang, Xinyuan ^{[1
,10
]}

Wong, Samuel Zheng Hao ^{[1
,11
]}

Joseph, Jessica ^{[11
]}

Dore, Louis C. ^{[12
,13
,14
]}

Dong, Qiang ^{[4
]}

Zheng, Wei ^{[15
]}

Jin, Peng ^{[16
]}

Wu, Hao ^{[9
]}

Shen, Bin ^{[7
]}

Zhuang, Xiaoxi ^{[17
]}

He, Chuan ^{[12
,13
,14
]}

Liu, Kai ^{[3
]}

Song, Hongjun ^{[1
,5
,6
,11
,18
,19
,20
]}

Ming, Guo-li ^{[1
,6
,11
,18
,20
]}

机构：

[1] Univ Penn, Perelman Sch Med, Mahoney Inst Neurosci, Dept Neurosci, Philadelphia, PA 19104 USA

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[3] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Div Life Sci, Hong Kong, Hong Kong, Peoples R China

[4] Fudan Univ, Huashan Hosp, State Key Lab Med Neurobiol, Dept Neurol, Shanghai 200040, Peoples R China

[5] Johns Hopkins Univ, Sch Med, Human Genet Pregrad Program, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Biochem Cellular & Mol Biol Grad Program, Baltimore, MD 21205 USA

[7] Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China

[8] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[9] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

[10] Fudan Univ, Sch Basic Med Sci, Shanghai 200040, Peoples R China

[11] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Grad Program, Baltimore, MD 21205 USA

[12] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[13] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[14] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA

[15] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA

[16] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA

[17] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA

[18] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA

[19] Univ Penn, Perelman Sch Med, Epigenet Inst, Philadelphia, PA 19104 USA

[20] Univ Penn, Perelman Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA

来源：

NEURON | 2018年 / 97卷 / 02期

基金：

中国国家自然科学基金;

关键词：

MESSENGER-RNA METHYLATION; SINGLE-NUCLEOTIDE-RESOLUTION; EPIGENETIC REGULATION; SENSORY NEURONS; DISTINCT MODES; HITS-CLIP; FAT MASS; GROWTH; MECHANISMS; STEM;

D O I：

10.1016/j.neuron.2017.12.036

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

N-6 -methyladenosine (m(6)A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m(6)A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m(6)A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m(6)A-CLIP mapping further reveals a dynamic m(6)A landscape in the adult DRG upon injury. Loss of either m(6)A methyltransferase complex component Mettl14 or m(6)A-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.

引用

页码：313 / +

页数：19

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