Molecular Tweaking of Nitrogen Use Efficiency: Key to Sustainable Agriculture

Nitrogen use efficiency (NUE) is a central determinant of sustainable crop production, yet its improvement remains constrained by the complex integration of nitrogen uptake, assimilation, transport, remobilization, and signalling with plant growth and development. This review provides a comprehensive synthesis of the molecular and physiological basis of NUE in cereal systems, with particular emphasis on the coordination between nitrogen metabolism and yield formation. We examine key thematic areas including (i) nitrogen acquisition and assimilation pathways, (ii) long-distance transport and internal recycling mechanisms, (iii) regulatory networks governing nitrate signalling, and (iv) the genetic basis of NUE shaped by modern breeding. In this context, the legacy of the Green Revolution is critically evaluated, highlighting how semi-dwarf, fertilizer-responsive cultivars contributed to high yield potential while simultaneously reinforcing dependence on external nitrogen inputs and constraining intrinsic NUE. Recent advances in molecular biology are discussed, including chromatin-level regulation, promoter engineering, and genome-editing approaches, with a focus on their capacity to modulate nitrogen-responsive pathways without compromising productivity. Collectively, current evidence indicates that NUE cannot be substantially improved through single-gene manipulation alone, but instead requires coordinated optimization of interconnected regulatory networks controlling both nitrogen metabolism and plant development. We conclude that future progress in NUE improvement will depend on integrative strategies combining functional genomics, precise genome engineering, and field-based validation to develop high-yielding crop varieties capable of maintaining productivity under reduced nitrogen inputs.