SERBP1–PCIF1 complex–controlled m6Am modification in S1HLGlu neurons is required for neuropathic pain in mice

ABSTRACT: Nerve injury-induced changes in pain-associated genes contribute to genesis of neuropathic pain and comorbid anxiety. Phosphorylated CTD interacting factor-1 (PCIF1)-triggered N6, 2′-O-dimethyladenosine (m6Am) mRNA modification represents an additional layer of gene regulation. However, the role of PCIF1 in these disorders is elusive. Here, we report PCIF1 is increased in glutamatergic neurons of primary somatosensory cortex hindlimb (S1HLGlu) in neuropathic pain mouse with anxiety, but not inflammatory pain or anxiety alone. Serpine-1 mRNA-binding protein-1 (SERBP1) is identified as a PCIF1 cofactor, their complex contributes to m6Am deposition onto mRNA. Blocking increase in SERBP1-PCIF1 in S1HLGlu abolishes m6Am gain in maf1 homolog, negative regulator of RNA polymerase III (Maf1), elevates MAF1 level, and mitigates neuropathic pain and anxiety. Conversely, mimicking this increase adds m6Am onto Maf1, reduces MAF1, leads to comorbidity symptoms. These findings highlight m6Am significance in neuropathic pain-anxiety comorbidity and identify S1HLGlu SERBP1–PCIF1 as a potential therapeutic target.

ORGANISM(S): Homo Sapiens Mus Musculus

SUBMITTER: Zhiqiang Pan  

PROVIDER: PXD065634 | iProX | Mon Jun 30 00:00:00 BST 2025

REPOSITORIES: iProX