CDS-localized m6A drives co-translational RNA decay to relieve biotic and abiotic endoplasmic reticulum stresses.

The 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 co-localizes 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 defence.