Supply in aerobic soils15, mutant Rht-B1b allele affects both underlying and N-regulated wheat 15NO – uptake (Fig. 1f). Hence, DELLA accumulation confers combined semi-dwarfism, 3 decreased growth N-response, and decreased N uptake on GRVs. In consequence, achievement of higher GRV yield demands environmentally damaging N fertiliser inputs16. Improvement of new GRVs that remain high-yield with reduced N supply is thus an urgent international sustainable agriculture goal2,17. We consequently analysed GRV growth-metabolism integration, reasoning that our discoveries may well in turn enable development of new GRVs possessing enhanced NUE.Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsDimethyl sulfone site OsGRF4 promotes rice GRV NH4+ uptakeWe discovered 3-fold variation within the 15NH4+ uptake rates of 36 sd1-containing indica rice varieties and SD1-containing NJ6 manage (Fig. 2a), then crossed NM73 (having the highest price; Fig. 2a) with NJ6 (recurrent parent) to produce a BC1F2 population. Quantitative trait locus (QTL) evaluation of 15NH4+ uptake rates revealed two LOD-score peaks (qNGR1 and qNGR2, Fig. 2b; Supplementary Info Table 1). While the NM73 qngr1 allele coincides in map position with sd17,eight, the molecular identity on the NM73 qngr2 allele, associated with increased 15NH4+ uptake rates, was unknown. Positional mapping next located qngr2 to OsGRF4180 (Extended Information Fig. 1a), suggesting a previously unknown function in NH4+ uptake regulation. Because a NM73 (OsGRF4ngr2) allele heterozygote has a greater rate than a NJ6 (OsGRF4NGR2) allele homozygote (Extended Data Fig. 1b), OsGRF4ngr2 semi-dominantly increases NH4+ uptakes. An NJ6-OsGRF4ngr2 isogenic line accordingly exhibited elevated NH4+ uptake rates (versus NJ6; Fig. 2c), and increased OsGRF4 mRNA and OsGRF4 protein abundances (Fig. 2d; Extended Data Fig 1c). In addition, anti-OsGRF4 RNAi reduced the higher 15NH4+ uptake price of NJ6-OsGRF4ngr2,Nature. Author manuscript; accessible in PMC 2019 February 15.Li et al.Pagewhereas transgenic expression of OsGRF4ngr2 mRNA from its native promoter increased 15NH + uptake (Fig. 2c; Extended Data Fig 1c). Overexpression of either OsGRF4NGR2 or 4 OsGRF4ngr2 mRNA from the constitutive rice Actin1 promoter conferred elevated 15NH4+ uptake prices on NJ6 (Fig. 2c; Extended Data Fig. 1c). Thus, OsGRF4ngr2 is equivalent to qngr2, confers an enhanced 15NH4+ uptake price on NM73, and counteracts the repressive effects of sd1-mediated SLR1 accumulation.Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsOsGRF4NGR2 (NJ6) and OsGRF4ngr2 (NM73) allelic comparisons revealed several SNPs (single nucleotide polymorphisms; Extended Information Fig. 1a, d), two of which (g.1187TA and g.1188CA in exon three) avoid OsmiR396-mediated cleavage of OsGRF4ngr2 mRNA180, as a result growing OsGRF4 mRNA and OsGRF4 abundance (Fig. 2d; Extended Information Fig. 1c) and promoting NH4+ uptake. Nevertheless, selection RD23 (although lacking 1187A and 1188A) also displays a high 15NH4+ uptake rate (Fig. 2a; Extended Data Fig. 1d), and shares 3 OsGRF4 promoter SNPs (g.-884TA, g.-847CT and g.-801CT; Extended Data Fig. 1a, d) with NM73. In all, we detected 3 OsGRF4 promoter haplotypes (A, as in 9311 and also other indica varieties; B, with -884A, -847T and -801T, as in NM73 and RD23; and C, prevalent in japonica germplasm; Extended Information Fig. 1d). Interestingly, OsGRF4 mRNA abundance is higher in haplotype B-containing varieties TZZL1 and RD23 (Extended Data Fig. 1d) than in elite variet.