WTAP-mediated m6A methylation stabilizes pIgR mRNA and attenuates smoke-induced epithelial inflammation and apoptosis
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.
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BibTeX
@article{li2026wtapmediated,
title = {{WTAP-mediated m6A methylation stabilizes pIgR mRNA and attenuates smoke-induced epithelial inflammation and apoptosis}},
author = {Jiaqi Li and Shengyu Huang and Guanghua Guo},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117958},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03341-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - WTAP-mediated m6A methylation stabilizes pIgR mRNA and attenuates smoke-induced epithelial inflammation and apoptosis
AU - Jiaqi Li
AU - Shengyu Huang
AU - Guanghua Guo
PY - 2026
DA - 2026/10/24
JO - iScience
DO - 10.1016/j.isci.2026.117958
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03341-9
AB - 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.
SN - 2589-0042
ER -