SNi公司
神经病理性疼痛
下调和上调
信使核糖核酸
血管内皮生长因子A
细胞生物学
生物
内分泌学
内科学
医学
神经科学
生物化学
血管内皮生长因子
基因
血管内皮生长因子受体
水解
酸水解
作者
Ting Xu,Jing Wang,Yan Wang,Jia‐Yan Wu,Weicheng Lu,Meng Lv,Subo Zhang,Dan Xie,Wenjun Xin,Jingdun Xie
标识
DOI:10.1002/advs.202303113
摘要
N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional machinery with extensive existence for RNA modification, plays versatile roles in various cellular processes and functions. However, the molecular mechanism by which ac4C modification mediates neuropathic pain remains elusive. Here, it is found that the enhanced ac4C modification promotes the recruitment of polysome in Vegfa mRNA and strengthens the translation efficiency following SNI. Nerve injury increases the expression of NAT10 and the interaction between NAT10 and Vegfa mRNA in the dorsal horn neurons, and the gain and loss of NAT10 function further confirm that NAT10 is involved in the ac4C modification in Vegfa mRNA and pain behavior. Moreover, the ac4C-mediated VEGFA upregulation contributes to the central sensitivity and neuropathic pain induced by SNI or AAV-hSyn-NAT10. Finally, SNI promotes the binding of HNRNPK in Vegfa mRNA and subsequently recruits the NAT10. The enhanced interaction between HNRNPK and NAT10 contributes to the ac4C modification of Vegfa mRNA and neuropathic pain. These findings suggest that the enhanced interaction between HNRNPK and Vegfa mRNA upregulates the ac4C level by recruiting NAT10 and contributes to the central sensitivity and neuropathic pain following SNI. Blocking this cascade may be a novel therapeutic approach in patients with neuropathic pain.
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