Rice (Oryza sativa) provides >20% of the consumed calories in the human diet. However, rice is also a leading source of dietary cadmium (Cd) that poses a serious threat to human health. Deciphering the genetic network that underlies the grain-Cd accumulation will benefit the development of low-Cd rice to mitigate the effects of Cd accumulation in the rice grain. In this study, we identified a QTL-gene, OsCS1, that is allelic to OsMTP11 and encodes a protein sequestering Cd in the leaf during vegetative growth and preventing Cd from being translocated to the grain after heading in rice. OsCS1 is predominantly expressed in leaf vascular parenchyma cells, where it binds to a vacuole sorting receptor protein OsVSR2 and is translocated intracellularly from the trans-Golgi network (TGN) to pre-vacuolar compartments (PVCs) and then to the vacuole. In this trafficking process, OsCS1 actively transports Cd into the endomembrane system and eventually sequesters it in vacuoles. There are natural variations in the promoter of OsCS1 between the indica and japonica rice subspecies. Duplication of a G-box-like motif in the promoter region of the superior allele of OsCS1 from indica rice enhances the binding of the transcription factor OsIRO2 to the OsCS1 promoter, thereby promoting OsCS1 expression. Introgression of this allele into commercial rice varieties could significantly lower grain-Cd levels compared to the inferior allele present in japonica rice. Our findings fill a gap in the genetic control of leaf-to-grain Cd translocation and provide a novel gene and its superior allele for the genetic improvement of low-Cd variety in rice.
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