Selective recruitment of NAT10-catalyzed ac4C-modified mRNAs into stress granules by poly(A)-binding protein promotes mRNA stability and plant heat-stress tolerance.

Global warming poses a considerable threat to crop production, making heat stress a challenge in agriculture, yet how epitranscriptomic modifications contribute to plant heat-stress responses remains to be explored. This study reveals the role of phase separation in plant heat-stress tolerance and shows that N-acetyltransferase 10 (NAT10), which encodes a cytosine N4 acetyltransferase, contributes to heat resistance. We found that NAT10 interacts with polyadenylate-binding protein (PABP), which contains intrinsically disordered regions, thereby facilitating the selective recruitment of ac4C-modified mRNAs into PABP-mediated condensates. Integrative transcriptome-wide analysis, combining ac4C acetylome profiling with stress-granule-enriched transcript sequencing, revealed that detoxification-related mRNAs, including those encoding the cytochrome P450, phenylalanine ammonia-lyase, glutathione S-transferase, and heat shock 70 protein families, preferentially accumulate within these condensates. This accumulation maintains their stability and prevents stress-induced degradation. Conversely, loss of PABP function impairs the recruitment of ac4C-modified detoxification-related transcripts into stress granules, thereby promoting their degradation under heat stress. In summary, our findings identify a stress-responsive NAT10-PABP-ac4C axis that promotes phase separation to stabilize ac4C-modified mRNAs under heat stress. By recruiting detoxification-related transcripts into stress granules, this axis ensures mRNA stability under environmental stress, offering new insights for enhancing crop stress resilience.