Nitrogen is essential for plant growth. It is required to build amino acids, proteins, nucleic acids, chlorophyll, and many other molecules that sustain photosynthesis and development. Modern agriculture has dramatically increased crop yields through the widespread use of nitrogen fertilizers, but plants typically absorb only about half of the nitrogen applied to fields. The remainder can leach into rivers and groundwater, fuel harmful algal blooms, and contribute to emissions of nitrous oxide, a greenhouse gas far more powerful than carbon dioxide over a century-long period.

The economic and geopolitical costs of fertilizer have also intensified interest in improving nitrogen-use efficiency. Manufacturing and transporting fertilizer requires substantial energy, while the storage and movement of nitrogen-based products can pose safety risks. Developing crops that capture and assimilate more nitrogen from the soil could allow farmers to maintain productivity while applying less fertilizer, potentially reducing costs and limiting pollution.

The NYU-led study focused on how plants interpret different nitrogen concentrations and forms. Plants absorb inorganic nitrogen, primarily nitrate and ammonium, from the soil and convert it into organic nitrogen compounds such as amino acids. These organic molecules can then be transported through the plant, stored, or used to build the cellular components needed for growth. Because nitrogen uptake and assimilation require considerable energy, plants need a feedback system that prevents them from continuing to acquire nitrogen after their internal supplies are sufficient.

Using Arabidopsis thaliana, a small flowering plant widely used as a model organism, the researchers examined gene activity across different nitrogen doses. This approach allowed them to distinguish genes responding simply to nitrogen exposure from those responding to specific levels or forms of nitrogen. The analysis led the team to HHO5, a transcription factor—a regulatory protein that binds to DNA and influences the activity of other genes. HHO5 emerged as a central component of the plant’s nitrogen-satiety response.

The researchers found that HHO5 expression increased when plants accumulated sufficient organic nitrogen. Once activated, the protein performed two complementary functions. It stimulated genes involved in organic nitrogen signaling and amino acid metabolism, helping the plant process and use the nitrogen already available. At the same time, it reduced the expression of genes responsible for absorbing more inorganic nitrogen from the soil. In effect, HHO5 acts as a molecular message that tells the plant, “The nitrogen supply is sufficient; stop bringing in more.”

The protein’s behavior depended partly on its interaction with another transcription factor, WRKY21. When HHO5 acted alone, it repressed genes associated with inorganic nitrogen uptake. When it partnered with WRKY21, however, the regulatory complex activated genes involved in organic nitrogen responses and plant defense. This switch-like behavior helps explain how the same protein can coordinate apparently opposite outcomes: limiting further nitrogen acquisition while increasing the plant’s ability to metabolize and respond to nitrogen already inside its tissues.

To investigate this mechanism, the scientists used a genomics method called DoubleTARGET. The technique links two regulatory proteins of interest to different fluorescent markers, enabling researchers to isolate plant cells containing high levels of both proteins. RNA sequencing can then reveal which genes respond specifically to the protein pair. Cells enriched in both HHO5 and WRKY21 showed increased activity in genes associated with organic nitrogen signaling and defense responses, supporting the idea that the two factors operate together as a functional regulatory module.

The strongest evidence came from plants lacking HHO5. Under particular nitrogen conditions, these mutant Arabidopsis plants absorbed nearly three times more nitrogen than plants with normal HHO5 activity. The result indicates that removing or weakening the regulator can release the molecular brake on inorganic nitrogen uptake. Although the finding does not yet demonstrate improved agricultural performance in food crops, it suggests that manipulating the HHO5 pathway could be a route toward plants that continue absorbing available nitrogen for longer or assimilate it more effectively.

The researchers caution that nitrogen metabolism is tightly connected to plant growth, energy use, stress responses, and environmental conditions. Simply increasing nitrogen uptake may not be beneficial if a plant cannot convert that nitrogen into biomass or if excessive accumulation causes physiological problems. Future work will need to determine whether modifying HHO5 can improve nitrogen-use efficiency in crops such as wheat, maize, rice, or vegetables without reducing yield, nutritional quality, or resilience.

The study, led by Gloria Coruzzi at NYU and Mariana Obertello of Argentina’s Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, provides a detailed model of how plants establish nitrogen satiety. By revealing how HHO5 changes from a repressor of inorganic nitrogen uptake into an activator of organic nitrogen signaling when paired with WRKY21, the research identifies a promising target for crop engineering. NYU has filed a patent application covering the findings, which could support future efforts to develop “gluttonous” crops capable of capturing more nitrogen while helping farmers reduce fertilizer use and its environmental consequences.

Subject of Research: Plant nitrogen sensing, nitrogen-use efficiency, gene regulation, Arabidopsis thaliana

Article Title: HHO5 orchestrates dose-dependent feedback regulation of organic versus inorganic nitrogen signaling in Arabidopsis

News Publication Date: 30-Jul-2026

Web References: https://doi.org/10.1093/plcell/koag201 ; https://as.nyu.edu/faculty/gloria-coruzzi.html?challenge=d06e90d7-4d8f-4b88-9d8c-10b73beb60f1

References: The Plant Cell, DOI: 10.1093/plcell/koag201

Image Credits: Will Hinckley, NYU

Keywords: HHO5, WRKY21, nitrogen uptake, nitrogen-use efficiency, plant biology, Arabidopsis thaliana, plant genetics, gene expression, fertilizers, crop science, sustainable agriculture

Maize, one of the world’s staple crops, has undergone extensive domestication and selective breeding over millennia. This process, while improving yield and adaptability, has inadvertently led to a sharp decline in seed protein content—a vital component for human and animal nutrition. Scientists have long sought to understand the genetic and biochemical underpinnings of this decline to design strategies that restore or even enhance seed protein levels in modern maize varieties.

At the core of protein biosynthesis in plants lies nitrogen assimilation and the interconversion of key amino acids such as glutamine and asparagine. These amino acids serve as nitrogen carriers, and their abundance is tightly linked to overall protein content. Asparagine, synthesized from glutamine via the enzyme asparagine synthase, plays a pivotal role in nitrogen transport and storage, highlighting the importance of nitrogen metabolism in seed quality.

Previous studies had already identified a superior teosinte haplotype of the gene encoding asparagine synthase 4 (ASN4), which positively influences protein content. Building on this foundation, the new research team turned their attention to the glutamine synthesis pathway, seeking to uncover complementary genetic variants that could synergize with ASN4 to further boost nitrogen assimilation.

Using advanced genetic mapping and molecular cloning techniques, the researchers identified and isolated a novel gene they named teosinte high protein 3 (THP3). This gene encodes glutamate-oxaloacetate transaminase 1 (GOT1), a critical enzyme orchestrating nitrogen assimilation and the balance between carbon and nitrogen in plant metabolism. GOT1 catalyzes transamination reactions vital for amino acid biosynthesis, making it a logical target for improving nitrogen use efficiency.

The investigation revealed that the THP3 gene from teosinte, referred to as the THP3-T allele, possesses unique natural variations not present in modern maize alleles. These variations significantly enhance both the expression level of the gene and the enzymatic activity of GOT1, suggesting a potent capacity to increase amino acid production and, by extension, seed protein content.

Functional validation experiments lend compelling support to the superiority of the THP3-T allele. Overexpressing THP3-T in maize not only significantly elevated seed protein content but also altered the carbon-nitrogen composition of the seeds in beneficial ways. In stark contrast, the contemporary THP3-B allele native to modern maize failed to elicit such effects, underscoring the lost potential in domesticated germplasm.

Evolutionary analyses indicate that the THP3-T allele was subject to negative selection during the domestication and improvement of maize, likely because breeding efforts prioritized traits such as yield and stress resistance over seed nutritional quality. This phenomenon illustrates a classic case of genetic trade-offs in crop domestication, where beneficial alleles in one context become rare or lost in another.

The study goes beyond single-gene interventions by exploring the combined effect of THP3-T with the previously identified superior allele for ASN4, dubbed THP9-T. Remarkably, pyramiding these two teosinte alleles into elite maize hybrids produced a synergistic enhancement in both seed and whole-plant protein levels without detrimental impacts on grain yield. This dual-gene strategy offers a compelling blueprint for simultaneous improvement of crop nutrition and productivity.

These discoveries hold substantial promise for tackling global challenges related to malnutrition and sustainable agriculture. By reintroducing rare yet powerful alleles from wild relatives, breeders can enhance the nutritional value of maize, a vital calorie source for billions, while preserving agronomic performance. This approach could lessen reliance on synthetic fertilizers and protein supplements, aligning with environmental and economic goals.

Mechanistically, the study uncovers how the THP3-T allele amplifies GOT1 activity, optimizing nitrogen assimilation pathways and promoting the generation of nitrogen-rich amino acids. This biochemical enhancement cascades into elevated synthesis of seed storage proteins, which are crucial for both seedling vigor and human dietary quality. Importantly, the modifications do not disrupt carbon metabolism, maintaining overall plant health and yield stability.

The research offers a rare glimpse into the complex interplay between domestication, genetics, and plant metabolism. It highlights the untapped genetic reservoirs in crop wild relatives, emphasizing that traits lost through domestication can be reclaimed to address modern agricultural needs. As gene editing and advanced breeding technologies evolve, such allele mining from teosinte and other wild species is poised to become a cornerstone of next-generation crop improvement.

Looking forward, the integration of these findings into commercial breeding programs could pave the way for maize varieties with substantially enhanced protein content, reducing malnutrition in vulnerable populations worldwide. The study also establishes a framework for similar efforts in other crops where nutrition has been compromised by historical breeding priorities.

In conclusion, this research not only advances our fundamental understanding of nitrogen assimilation and protein biosynthesis in maize but also demonstrates a viable, powerful strategy for enhancing seed nutrition. Reintroducing beneficial alleles from teosinte, a wild ancestor, holds transformative potential for the future of sustainable agriculture and food security, bridging the gap between ancient genetic wisdom and modern crop science.

Subject of Research: Enhancing nitrogen assimilation and seed protein content in maize through natural alleles from teosinte.

Article Title: Teosinte alleles enhance nitrogen assimilation and seed protein in maize.

Article References:
Huang, Y., Zhu, Y., Cui, Y. et al. Teosinte alleles enhance nitrogen assimilation and seed protein in maize. Nature (2026). https://doi.org/10.1038/s41586-026-10575-8

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41586-026-10575-8