NAT10 recruits PABP to compartmentalize ac4C-modified mRNAs into stress granules and enhance mRNA stability during plant heat thermotolerance

The phenomenon of global warming and the consequent rise in global temperatures are of such significance that they pose a considerable threat to the successful cultivation of crops. As a result, heat stress has become a critical challenge in the field of agriculture. The present study has revealed the critical role of phase separation in plant heat stress tolerance and has demonstrated that N-acetyltransferase 10 ( NAT10 ), which is responsible for the encoding of the cytosine N4 acetyltransferase protein, contributes to heat resistance. The interaction of NAT10 with polyadenylate-binding protein (PABP), which contains intrinsically disordered regions (IDRs), has been shown to facilitate the selective recruitment of ac4C-modified mRNAs into PABP-mediated condensates. Through comprehensive analysis of the entire transcriptome and the mapping of ac4C acetylation marks and SG-enriched transcripts, it was identified that detoxification-related mRNAs, including those of the cytochrome P450, phenylalanine-lyase, glutathione S-transferase and heat shock 70 protein families, preferentially accumulate within these condensates. This accumulation contributes to the maintenance of their stability and the prevention of stress-induced degradation. Conversely, the loss of PABP has been shown to impede the recruitment of ac4C-modified detoxification-related transcripts into stress granules, consequently leading to the destabilization of these mRNAs under heat stress conditions. In summary, our findings identify a stress-responsive NAT10-PABP-ac4C axis that orchestrates phase separation to stabilize ac4C-modified mRNAs under heat stress. The recruitment of detoxification-related transcripts into stress granules by this mechanism ensures mRNA stability, offering insights to enhance crop resilience under environmental stress.