Faculty, Staff and Student Publications
Language
English
Publication Date
11-28-2023
Journal
Cell Reports
DOI
10.1016/j.celrep.2023.113401
PMID
37943660
Abstract
TRPA1 is pivotal in cold hypersensitivity, but its regulatory mechanisms in inflammatory cold hyperalgesia remain poorly understood. We show here that the upregulation of SUMO1-conjugated protein levels in a complete Freund's adjuvant (CFA)-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA, and its SUMOylation, upregulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm. Moreover, we find that wild-type hnRNPA1 viral infection in dorsal root ganglia neurons, and not infection with the SUMOylation-deficient hnRNPA1 mutant, can rescue the reduced ability of hnRNPA1-knockdown mice to develop inflammatory cold pain hypersensitivity. These results suggest that hnRNPA1 is a regulator of TRPA1 mRNA stability, the capability of which is enhanced upon SUMO1 conjugation at lysine 3 in response to peripheral inflammation, and the increased expression of TRPA1 in turn underlies the development of chronic inflammatory cold pain hypersensitivity.
Keywords
Ganglia, Spinal, Hyperalgesia, Chronic Pain, Freund's Adjuvant, Mice, Animals, RNA, Messenger, TRPA1 Cation Channel, Inflammation, Sumoylation, Heterogeneous Nuclear Ribonucleoprotein A1, Cryopyrin-Associated Periodic Syndromes, CP: Neuroscience, TRPA1 expression, cold hypersensitivity in chronic inflammatory pain, hnRNPA1 SUMOylation, mRNA stability
Published Open-Access
yes
Recommended Citation
Zhang, Qiao; Weng, Weiji; Gu, Xiaokun; et al., "hnRNPA1 SUMOylation Promotes Cold Hypersensitivity in Chronic Inflammatory Pain by Stabilizing TRPA1 mRNA" (2023). Faculty, Staff and Student Publications. 3426.
https://digitalcommons.library.tmc.edu/uthmed_docs/3426
Graphical Abstract