Open AccessN 6 ‐Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons
Author(s) -
Li Yize,
Guo Xinying,
Sun Linlin,
Xiao Jifang,
Su Songxue,
Du Shibin,
Li Zhen,
Wu Shaogen,
Liu Weili,
Mo Kai,
Xia Shangzhou,
Chang YunJuan,
Denis Daniel,
Tao YuanXiang
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201902402
Subject(s) - neuropathic pain , demethylase , nerve injury , dorsal root ganglion , downregulation and upregulation , medicine , peripheral nerve injury , histone methyltransferase , endocrinology , gene expression , neuroscience , histone , pharmacology , anesthesia , sensory system , chemistry , biology , gene , biochemistry , sciatic nerve
Nerve injury‐induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N 6 ‐methyladenosine (m 6 A) modification of RNA represents an additional layer of gene regulation. Here, it is reported that peripheral nerve injury increases the expression of the m 6 A 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 m 6 A 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 m 6 A 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.