CDS-localized m6A drives co-translational RNA decay to relieve biotic and abiotic endoplasmic reticulum stresses
12 affiliations
- 1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
- 2Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
- 3Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
- 4These authors contributed equally.
- 5Xenohelix Research Institute, Incheon 21984, Republic of Korea
- 6CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China
- 7Department of Medical Physiology, Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807, USA
- 8Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
- 9Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
- 10Former: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
- 11Institute of Emerging Agricultural Technology, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, 518107, China.
- 12Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, 518107, China.
Abstract
Endoplasmic reticulum (ER) mitigates stress typically through unfolded protein response (UPR) and ER-associated degradation (ERAD) pathways, yet post-transcriptional regulation of ER stress remains poorly defined. N6-methyladenosine (m6A) modification, predominantly enriched near stop codons, can govern mRNA fates via P-bodies or stress granules in stress conditions. m6A also occurs within coding sequences (CDS-m6A), but its role remains unappreciated in plants. Here we demonstrate that m6A ablation sensitizes Arabidopsis ER stress despite normal UPR and ERAD activities. Mechanistically, CDS-m6A colocalizes with ribosome stalling sites and directs co-translational RNA decay (CTRD). Under stress, activation of m6A-triggered CTRD accelerates clearance of ER-engaged transcripts, thereby alleviating translational overload. During Geminivirus infection, which increases translational demand on ER, m6A-triggered CTRD also targets viral RNAs, restricting their accumulation, translation and disease progression. Thus, CDS-m6A functions as a pivotal regulator of ER-linked RNA surveillance, establishing an organelle-specific mechanism that integrates RNA stability, protein homeostasis, and antiviral defense.
Related
- A delayed translocation into the endoplasmic reticulum controls the post-translational modifications of PD-L1
- Pathogenesis of Calcium Oxalate Kidney Stones, Interactions Among Mitochondria, NADPH Oxidase and Endoplasmic Reticulum
- Minor Phytocannabinoids as Candidate Multi-Target Modulators of Endoplasmic Reticulum Stress-Linked Proteostasis Failure in Alzheimer’s Disease: A Mechanistic Review
- PACE4 Regulates Apoptosis in Human Prostate Cancer Cells via Endoplasmic Reticulum Stress and Mitochondrial Signaling Pathways [Retraction].
- A conserved antioxidant defense at the endoplasmic reticulum membrane
BibTeX
@article{zhong2026cdslocalized,
title = {{CDS-localized m6A drives co-translational RNA decay to relieve biotic and abiotic endoplasmic reticulum stresses}},
author = {Songxiao Zhong and Taerin Oh and Xindi Li and Jinming Zhang and Suk Won Choi and Chuyun Gao and Xu Peng and Juan Dong and Chuan He and Xiuren Zhang},
journal = {Nature plants},
year = {2026},
month = may,
doi = {10.1038/s41477-026-02299-4},
url = {https://doi.org/10.1038/s41477-026-02299-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CDS-localized m6A drives co-translational RNA decay to relieve biotic and abiotic endoplasmic reticulum stresses
AU - Songxiao Zhong
AU - Taerin Oh
AU - Xindi Li
AU - Jinming Zhang
AU - Suk Won Choi
AU - Chuyun Gao
AU - Xu Peng
AU - Juan Dong
AU - Chuan He
AU - Xiuren Zhang
PY - 2026
DA - 2026/05/08
JO - Nature plants
DO - 10.1038/s41477-026-02299-4
UR - https://doi.org/10.1038/s41477-026-02299-4
AB - Endoplasmic reticulum (ER) mitigates stress typically through unfolded protein response (UPR) and ER-associated degradation (ERAD) pathways, yet post-transcriptional regulation of ER stress remains poorly defined. N6-methyladenosine (m6A) modification, predominantly enriched near stop codons, can govern mRNA fates via P-bodies or stress granules in stress conditions. m6A also occurs within coding sequences (CDS-m6A), but its role remains unappreciated in plants. Here we demonstrate that m6A ablation sensitizes Arabidopsis ER stress despite normal UPR and ERAD activities. Mechanistically, CDS-m6A colocalizes with ribosome stalling sites and directs co-translational RNA decay (CTRD). Under stress, activation of m6A-triggered CTRD accelerates clearance of ER-engaged transcripts, thereby alleviating translational overload. During Geminivirus infection, which increases translational demand on ER, m6A-triggered CTRD also targets viral RNAs, restricting their accumulation, translation and disease progression. Thus, CDS-m6A functions as a pivotal regulator of ER-linked RNA surveillance, establishing an organelle-specific mechanism that integrates RNA stability, protein homeostasis, and antiviral defense.
SN - 2055-0278
ER -