A cis-regulatory allele of ZmNPR1I spatially uncouples flowering from stalk-rot resistance in maize

Pleiotropic effects of adaptive genes frequently constrain crop improvement by coupling beneficial traits with unfavorable trade-offs. In maize, ZmCCT10 confers strong stalk-rot resistance but causes delayed flowering under long-day conditions, limiting its deployment in temperate breeding. Here, we identify qPss3 as a cis-regulatory locus that governs its downstream target gene, ZmNPR1I. The ZmNPR1I protein represses ZmCCT10 transcription and, together with ZmNPR1-3, facilitates ZmCCT10 protein degradation. The favorable qPss3^A5 allele reduces ZmNPR1I expression in leaves, relieving repression of ZmCCT10, ZmSPL32, and ID1, which collectively enhance ZCN8 expression to accelerate flowering. In roots, however, pathogen-induced activation of the resistant ZmCCT10^H5 allele largely bypasses qPss3 regulation, thereby preserving stalk-rot resistance. Introgression of qPss3^A5 into ZmCCT10^H5-containing maize germplasm restores flowering adaptation without compromising disease resistance, improving yield stability under disease pressure. Our work reveals a tissue-specific qPss3^A5-ZmNPR1I regulatory module that uncouples the developmental and immune functions of a pleiotropic adaptive gene, providing a general strategy for optimizing beneficial alleles in crop breeding.