Cadmium (Cd) contamination poses a serious threat to global food safety. As a toxic and carcinogenic heavy metal, cadmium can accumulate in agricultural soils through industrialization and urbanization before entering the human food chain. Rice is especially vulnerable because it absorbs more cadmium than other major cereal crops, making it one of the largest dietary sources of cadmium exposure for nearly half the world's population.
Although researchers have long sought to develop rice varieties with lower cadmium levels, existing approaches often reduce the uptake of essential nutrients or compromise crop growth and grain yield, limiting their practical use.
A single edit with broad effects
Addressing this challenge, a research team led by Dr. Sheng Huang and Jian Feng Ma from the Institute of Plant Science and Resources, Okayama University, Japan, together with Jiayang Li's group from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China, used precise base-editing technology to identify a beneficial point mutation in the rice metal transporter gene OsNramp5.
Through saturation mutagenesis targeting OsNramp5, the researchers screened hundreds of genome-edited rice lines to identify variants that accumulated less cadmium while maintaining normal manganese uptake and plant performance.
They discovered that replacing a single amino acid, isoleucine, with threonine at position 441 (OsNramp5I441T), produced the most promising result. Their findings were published in Proceedings of the National Academy of Sciences (PNAS).
How zinc shifts cadmium movement
The researchers generated more than 1,600 genome-edited rice lines using adenine and cytosine base editors and screened them for reduced cadmium accumulation. After identifying the most promising mutant, they carried out detailed physiological analyses, gene expression studies, protein localization experiments, yeast transport assays and field trials on cadmium-contaminated soil.
The results showed that the OsNramp5I441T mutation reduced cadmium accumulation in both shoots and grains without altering gene expression, protein abundance, cellular localization or grain yield. In field experiments, cadmium concentration in brown rice decreased by 48%, from 0.14 mg/kg in wild-type plants to 0.07 mg/kg in edited plants, while concentrations of essential micronutrients, including iron, manganese and zinc, remained unchanged.
Further investigation revealed why this single amino acid change was so effective. Although OsNramp5 was already known to transport manganese and cadmium, the researchers discovered that it also transports zinc. The I441T mutation increased the transporter's preference for zinc, allowing more zinc to accumulate in root cells.
This elevated zinc then competed with cadmium during root-to-shoot transport, reducing the movement of cadmium into the shoots and eventually the grains.
Rather than blocking cadmium uptake completely, the mutation selectively limited its translocation, solving a long-standing challenge of lowering grain cadmium without disrupting the plant's supply of essential minerals.
A breeding tool for safer rice
The study offers a practical solution for improving food safety through precision breeding. Existing strategies to reduce cadmium in rice, including soil amendments, water management or complete knockout of OsNramp5, can be costly, time-consuming or negatively affect plant growth because OsNramp5 also transports manganese, an essential nutrient.
By modifying only a single amino acid instead of disabling the entire gene, the researchers preserved normal plant growth, grain yield and the accumulation of essential micronutrients while substantially lowering cadmium levels.
"We have been working on cadmium accumulation in rice for more than 20 years and have identified several key genes involved in this process. Because OsNramp5 also transports essential metals, we aimed to alter its metal selectivity rather than eliminate its function, leading us to this successful point mutation," said Ma.
Overall, the discovery provides a valuable genetic resource for breeding rice varieties with safer grain and demonstrates how precise genome editing can overcome limitations that conventional breeding or gene knockout approaches cannot.
The researchers believe the newly identified OsNramp5I441T allele could accelerate the development of low-cadmium rice cultivars suitable for cultivation on mildly contaminated soils while maintaining productivity and nutritional quality.
"This mutation provides an effective strategy for reducing cadmium accumulation in rice grain without compromising yield or essential mineral nutrition, offering a promising approach for producing safer rice for consumers," Ma concluded.
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