GEOTranscriptomicsOryza sativaExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315654GEOGSEfalseIntegrated Multi-omics Analysis Reveals that Hybrid Rice Reprograms Carbon Metabolism to Confer Drought ResistanceDrought severely limits global rice production, and exploiting heterosis offers a promising route to improve drought resistance. However, the molecular mechanisms underlying drought resistant heterosis remain largely unknown. Here, we integrated multi-omics analyses of the flag leaves of elite hybrid rice Hanyou73 (HY73) and its parental lines, Hanhui3 (HH3) and Huhan7B (HH7B), during grain filling under drought. We uncover a non-additive effect (NAE)-driving carbon metabolic reprogramming fundamental to HY73’s superior performance under drought. Proteomic and metabolomic profiling revealed that HY73 preferentially channels photosynthetic carbon into a hybrid-specific monosaccharides–acetyl-CoA–lipid (MOS–AcCoA–Lipid) shunt, effectively diverting carbon into fatty acyls (FA) and prenol lipids (PR) that serve as vital energy reserves, membrane stabilizers, and precursors for hormone biosynthesis. Importantly, NAE-driving AcCoA accumulation correlates with elevated lysine acetylation (Kac) in HY73, establishing a bridge between metabolic flux and post-translational regulation. Acetylomic analyses pinpointed acetylation at lysine 155 (K155ac) on OsPGM3, a previously uncharacterized cytosolic phosphoglucomutase, as a pivotal regulatory switch. CRISPR/Cas9-mediated gene editing and biochemical assays demonstrated that drought-induced deacetylation activates OsPGM3, ensuring sufficient glucose-6-phosphate (G6P) for the lipid shunt while maintaining stable glucose-1-phosphate (G1P)-mediated sucrose export vital for yield potential. Thus, K155ac precisely fine-tunes OsPGM3 activity, acting as a post-translational checkpoint responsive to drought-induced carbon shifts. Together, our findings establish a hybrid-specific NAE–carbon flux–Kac regulatory axis that precisely balances drought adaptation with yield maintenance, offering new targets for breeding climate-resilient hybrid rice.2026/05/18GSE315654GSM9434062GSM9434051GSM9434050GSM9434061GSM9434060GSM9434049GSM9434059GSM9434048GSM9434047GSM9434058GSM9434057GSM9434046GSM9434045GSM9434056GSM9434055GSM9434054GSM9434053GSM943405235184315654Oryza sativa