Micro Proteins: A Novel Approach for Crop Improvement

Authors: Dr. Sabitha. N; Bhavani Saiesha. C; Narasimhulu. R; Naga Madhuri K.V; Reddi Sekhar. M
DIN
IJOEAR-OCT-2025-48
Abstract

Microproteins (miPs) are small proteins, typically under 20 kDa, that play crucial roles in protein-protein interactions by forming non-functional complexes, thus regulating targets in a dominant-negative manner. They are classified into cis-miPs, which arise from mRNA isoforms through alternative splicing or translation, and trans-miPs, which evolve from genome amplification and domain loss. miPs can interact homotypically with similar domains or heterotypically with compatible but non-identical domains, potentially broadening their regulatory functions. Initially identified in mice, numerous miPs have since been discovered in plants, particularly through computational methods, although few have been functionally characterized, with a focus on Arabidopsis thaliana. Recent advances in synthetic microproteins have demonstrated their potential in crop engineering by modulating physiological processes. In plants, miPs have been linked to various functions, including epidermal cell patterning during root hair and trichome development, light responses, leaf development, pigment biosynthesis, and floral development. The identification and characterization of miPs in economically important plants have been facilitated by improved genomic and molecular tools, highlighting their significance in plant physiology and agricultural applications.

Keywords
Microproteins (miPs) Crop Improvement Protein-Protein Interactions Crop Engineering Plant Development Cis-miPs Trans-miPs Dominant-Negative Regulation Synthetic Microproteins Arabidopsis thaliana
Introduction

Microproteins (miPs) are small proteins, typically ranging from 5 to 20 kDa, that play critical roles in plant growth and development by engaging in protein-protein interactions through a single domain (Kushwaha et al., 2022; Bs et al., 2023). The term 'microprotein' reflects their small size and negative regulatory properties, which are functionally analogous to microRNAs. miPs are thought to have evolved from gene duplications followed by domain loss, resulting in single-domain proteins that interact with and inhibit their multi-domain ancestral proteins (Straub et al., 2020). Consequently, miPs typically lack DNA-binding or activation domains and are unlikely to directly regulate transcription.

The first miP, a DNA binding inhibitor (Id) protein, was identified in mice as a 16 kDa helix-loop-helix (HLH) domain protein that inhibits the MyoD transcription factor to regulate muscle differentiation (Benezra et al., 1990). In plants, the LITTLE ZIPPER (ZPR) family was the first to be recognized as microproteins. Although TRYPTYCHON (TRY) was functionally characterized earlier, it was later classified as a miP due to its size and inhibitory function.

Microproteins are involved in a wide range of physiological processes, including metabolism, stress response, and the regulation of commercially vital traits like floral development and apical meristem maintenance. This positions both natural and synthetic miPs as powerful tools for crop bioengineering. With the advent of next-generation sequencing and advanced molecular tools, the discovery and characterization of miPs are accelerating, opening new avenues for agricultural innovation. FIGURE 1: Protein-miP interaction

Conclusion

Food security faces increasing challenges due to climate change and unsustainable agricultural practices, highlighting the urgent need for sustainable and innovative solutions. Microproteins are crucial regulators of various physiological processes in plants. Their small size makes them ideal candidates for developing synthetic microproteins that could enhance plant stress resilience and improve productivity. Gaining a deeper understanding of the regulatory mechanisms of microproteins is essential for harnessing their potential as biotechnological tools in agriculture.

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