WTAP-mediated m6A methylation stabilizes pIgR mRNA and attenuates smoke-induced epithelial inflammation and apoptosis.

Authors

Jiaqi Li, Shengyu Huang, Guanghua Guo

Published in

iScience. Volume 29. Issue 11. Pages 117958. Nov 20, 2026. Epub Oct 24, 2026.

Abstract

Smoke inhalation injury (SII) dramatically elevates burn patient mortality. Although N6-methyladenosine (m6A) methylation is emerging as a central epitranscriptomic regulator of lung inflammation and injury, its specific involvement in SII remains unknown. Using an in vivo mouse SII model and smoke extract-treated MLE-12 cells, we show that smoke exposure downregulates the m6A writer-complex component WTAP and reduces global m6A methylation. WTAP knockdown attenuates epithelial inflammation, apoptosis, and STAT3 activation. Integrating transcriptomics with weighted gene co-expression network analysis (WGCNA) and MeRIP-qPCR, we identify pIgR as a downstream target: WTAP modifies m6A methylation within the 756/772 region of pIgR mRNA, and its knockdown prolongs pIgR mRNA half-life and elevates pIgR expression. pIgR silencing reverses the protection conferred by WTAP knockdown. These findings define a WTAP/m6A/pIgR axis that shapes the early epithelial response to smoke inhalation and identifies WTAP as a candidate therapeutic target for SII.

PMID:
42967003
Bibliographic data and abstract were imported from PubMed on 01 Nov 2026.

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