N6 -Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons

Advanced Science
Yize LiYuan-Xiang Tao

Abstract

Nerve injury-induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N6-methyladenosine (m6A) modification of RNA represents an additional layer of gene regulation. Here, it is reported that peripheral nerve injury increases the expression of the m6A demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the Fto gene promoter. Mimicking this increase erases m6A in euchromatic histone lysine methyltransferase 2 (Ehmt2) mRNA (encoding the histone methyltransferase G9a) and elevates the level of G9a in DRG and leads to neuropathic pain symptoms. Conversely, blocking this increase reverses a loss of m6A sites in Ehmt2 mRNA and destabilizes the nerve injury-induced G9a upregulation in the injured DRG and alleviates nerve injury-associated pain hypersensitivities. FTO contributes to neuropathic pain likely through stabilizing nerve injury-induced upregulation of G9a, a neuropathic pain initiator, in primary sensory neurons.

References

Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Jan 14, 2004·The Journal of Pharmacology and Experimental Therapeutics·Md Harunor RashidHiroshi Ueda
Jan 13, 2005·Pain Management Nursing : Official Journal of the American Society of Pain Management Nurses·Chris Pasero
Feb 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carole Torsney, Amy B MacDermott
Feb 27, 2007·Cell·Tony Kouzarides
Mar 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jang-Su ParkYuan-Xiang Tao
Jan 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bernhard HeinkeJürgen Sandkühler
Apr 19, 2011·Genes & Development·Yoichi Shinkai, Makoto Tachibana
Oct 18, 2011·Nature Chemical Biology·Guifang JiaChuan He
May 12, 2012·Nature·Dan DominissiniGideon Rechavi
Jan 3, 2014·The Journal of Clinical Investigation·Ji-Tian XuYuan-Xiang Tao
Mar 26, 2014·Nature Reviews. Genetics·Ye FuChuan He
Apr 18, 2014·Anesthesiology·Brianna Marie LutzYuan-Xiang Tao
Sep 4, 2014·Nature Biotechnology·John G DoenchDavid E Root
Sep 23, 2014·Bioscience Reports·Pawan GulatiGiles S H Yeo
Dec 3, 2014·Nucleic Acids Research·Yue HuangCai-Guang Yang
May 6, 2015·Epigenomics·Lingli LiangYuan-Xiang Tao
Jun 30, 2015·Nature Methods·Bastian LinderSamie R Jaffrey
Sep 26, 2015·Genes & Development·Shengdong KeRobert B Darnell
Jun 29, 2016·RNA Biology·Samir AdhikariYun-Gui Yang

❮ Previous
Next ❯

Citations

Oct 6, 2020·Frontiers in Cell and Developmental Biology·Qiuyue XuBin Yuan
Oct 29, 2020·Journal of Experimental & Clinical Cancer Research : CR·Tiansheng LiYongguang Tao
Apr 9, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bi-Xin ZhengYuan-Xiang Tao
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Jun YuSheng-Jian Ji
Mar 7, 2021·Pain·Sfian Albik, Yuan-Xiang Tao
Jul 27, 2021·Frontiers in Genetics·Lei ZhangXianhu Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
transfection
PCR
RIP
ChIP
Assay
CLIP

Software Mentioned

Image Lab
pCLAMP
NIH Image J
SigmaStat
TFSEARCH

Related Concepts

Related Feeds

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.