In the relentless pursuit to enhance crop resilience amid escalating climate unpredictability, a groundbreaking study from rice researchers uncovers a sophisticated molecular switch that governs how plants respond to cold stress. At the heart of this discovery lies a deeper understanding of N^6-methyladenosine (m^6A), the most prevalent internal modification on eukaryotic messenger RNA, and how plants fine-tune proteins that ‘read’ this RNA mark to survive chilling temperatures. A new report published in Nature Plants presents the rice m^6A reader protein EVOLUTIONARILY CONSERVED C-TERMINAL REGION 3 (OsECT3) as a pivotal player whose activity is modulated via lysine acetylation — a post-translational modification — revealing an elegant biochemical strategy through which rice adapts to cold stress.
To contextualize this breakthrough, m^6A modifications on RNA have emerged as critical epitranscriptomic signals that regulate RNA metabolism, including stability, processing, and translation. Reader proteins that detect these m^6A marks act as molecular interpreters, directing downstream processes that govern gene expression programs. While the importance of these readers in plant development and stress responses has been increasingly recognized, the dynamic mechanisms controlling their activity remained obscure. The current study goes beyond this gap by characterizing how the acetylation status of OsECT3 fine-tunes its RNA-binding affinity — a modification-based on/off switch that holds sway over rice’s cold adaptation.
The researchers began their inquiry by identifying lysine acetylation as a reversible post-translational modification on OsECT3, which intriguingly reduces its affinity for m^6A-containing RNA sequences. This pinpointed a hitherto unknown layer of regulation, where chemical modification of the reader protein itself dictates its ability to shepherd crucial mRNAs. Importantly, at normal temperatures, this acetylation exists at a baseline level, but when plants confront cold stress, the acetylated fraction diminishes dramatically, unlocking OsECT3’s enhanced m^6A-binding capacity.
Digging deeper, the team revealed the involvement of a histone deacetylase enzyme, HDA705, whose expression is upregulated during cold exposure. This nuclear enzyme orchestrates the removal of acetyl groups from OsECT3, underscoring a direct enzymatic switch that sensitizes OsECT3 activity to environmental cues. This discovery not only showcases functional crosstalk between chromatin-modifying enzymes and RNA-binding proteins but also expands the functional repertoire of HDA705 beyond classical histone targets.
Intriguingly, the cold-triggered deacetylation of OsECT3 is compounded by metabolic factors. Under cold stress, the intracellular concentration of acetyl-CoA — the critical donor molecule for lysine acetylation — diminishes due to lowered activity of the ATP-citrate lyase A2 (ACLA2). This metabolic bottleneck further tips the balance in favor of OsECT3 deacetylation, tightly coupling cellular metabolic state with post-translational control of RNA recognition. Such integration between metabolism and RNA modification readers unveils a new axis in plant cold stress signaling.
The functional consequences of this regulatory axis become evident in the RNA landscape of cold-stressed rice. With enhanced binding of deacetylated OsECT3 to m^6A-modified transcripts, levels of cold-responsive mRNAs accumulate more robustly. This accumulation presumably stabilizes and regulates the translation of transcripts crucial for cold adaptation, empowering rice plants with a reinforced molecular arsenal to withstand chilling temperatures. The study thus reveals a nuanced, multifactorial scheme whereby dynamic acetylation controls the epitranscriptomic reader activity and shapes stress-responsive gene expression.
Methodologically, the researchers employed state-of-the-art biochemical and genetic approaches, including site-specific mutagenesis to alter lysine acetylation sites on OsECT3, mass spectrometry for acetylation mapping, RNA immunoprecipitation assays to assess m^6A binding, and cold tolerance assays in genetically engineered rice lines. These comprehensive analyses collectively validated the central hypothesis that OsECT3 acetylation is a reversible molecular switch modulated by cold stress.
The implications of this study resonate far beyond rice physiology. By connecting the dots between lysine acetylation, epitranscriptomic reader function, and metabolic status, the research charts a new course toward understanding how plants dynamically integrate environmental signals at multiple regulatory layers. The presence of evolutionarily conserved C-terminal regions among ECT proteins across plant species hints that such acetylation-mediated control may represent a widespread adaptive mechanism.
Furthermore, this insight opens novel avenues for agricultural innovation. With global climate change intensifying cold snaps and uneven weather patterns, engineering crops with optimized OsECT3 acetylation states or modulating the activity of key enzymes like HDA705 or ACLA2 may pave the way for developing cold-resilient cultivars. This molecular fine-tuning of epitranscriptomic readers has the potential to bolster yields and food security in vulnerable regions.
The research also invites a reevaluation of the canonical functions attributed to histone deacetylases. Traditionally confines to chromatin remodeling and transcriptional repression, enzymes like HDA705 now emerge as multifaceted regulators bridging chromatin landscapes, RNA modification readers, and metabolic signals. This expansion of functional horizons challenges scientists to rethink post-translational modification networks in plant stress biology.
Beyond cold stress, m^6A reader proteins modified by lysine acetylation might also be responsive to other abiotic or biotic stresses, suggesting a universal regulatory theme. Future studies may uncover whether similar acetylation dynamics regulate reader proteins in drought, salinity, or pathogen responses, further enriching our comprehension of plant adaptability.
In a broader biological context, this discovery spotlights the intricate mechanisms by which plants achieve environmental plasticity. The coupling of metabolic fluxes, enzymatic modifications, and epitranscriptomic regulation reflects evolutionary sophistication, enabling precise and rapid tuning of gene expression programs in response to changing climates.
Finally, this work emphasizes the importance of integrating multiple “omics” disciplines, including epitranscriptomics, proteomics, and metabolomics, to decode complex regulatory circuits. Such integrative frameworks are indispensable for unveiling functional relationships that single-layer analyses might overlook, accelerating translational breakthroughs in plant science and agriculture.
In summary, the elucidation of OsECT3 acetylation as a molecular rheostat for m^6A RNA binding under cold stress broadens our understanding of plant RNA biology and stress physiology. By uncovering how lysine acetylation modulates an m^6A reader to enhance cold tolerance, this study exemplifies the remarkable adaptability embedded within plant regulatory networks. As climate challenges mount, insights like these offer promising molecular tools to future-proof crops, ensuring sustainable agriculture and food security worldwide.
Subject of Research: Regulation of an m^6A RNA reader protein OsECT3 activity by lysine acetylation during cold stress response in rice.
Article Title: Regulation of m^6A RNA reader protein OsECT3 activity by lysine acetylation in the cold stress response in rice.
Article References:
Ma, N., Song, P., Liu, Z. et al. Regulation of m^6A RNA reader protein OsECT3 activity by lysine acetylation in the cold stress response in rice. Nat. Plants 11, 1165–1180 (2025). https://doi.org/10.1038/s41477-025-02013-w
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