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


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.

SUBMITTER: Li Y 

PROVIDER: S-EPMC7341103 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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N<sup>6</sup>-Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons.

Li Yize Y   Guo Xinying X   Sun Linlin L   Xiao Jifang J   Su Songxue S   Du Shibin S   Li Zhen Z   Wu Shaogen S   Liu Weili W   Mo Kai K   Xia Shangzhou S   Chang Yun-Juan YJ   Denis Daniel D   Tao Yuan-Xiang YX  

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200527 13


Nerve injury-induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N<sup>6</sup>-methyladenosine (m<sup>6</sup>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<sup>6</sup>A demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that bind  ...[more]

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