Integrated multilayer regulatory networks for arsenic (As) stress resilience in plants

• TFs regulate As uptake, transport, and redox by modulating transporters, detox genes, and antioxidants. • As stress signaling via ROS, Ca²⁺, MAPKs, and hormones activates TFs through phosphorylation for rapid gene control. • PTMs and PTReg modulate protein function and transcript diversity, enhancing As stress adaptation. • Collective integrated multilayer regulatory network of TFs, signaling, PTReg, and PTMs coordinates As detox and stress resilience in plants. Arsenic (As) toxicity severely impacts plant health, agricultural productivity, and food security. In response to stress, plants deploy intricate regulatory mechanisms that coordinate gene expression and defense strategies. Considerable progress has been made in understanding individual regulatory layers, including transcription factors (TFs), signaling cascades, post-transcriptional regulation (PTReg), and post-translational modifications (PTMs), and prior reviews have discussed aspects of their interplay (e.g., TF–signaling cross-talk, signaling–PTM interactions, or microRNA–TF regulation). However, in the context of As stress, a comprehensive synthesis that explicitly interlinks these layers into a single, dynamic framework is still lacking. This review aims to bridge that gap by exploring emerging insights into how TFs, signaling networks, PTReg, and PTMs collectively drive transcriptional reprogramming, thereby modulating As uptake, transport, detoxification, hormone signaling, and antioxidant defenses. By emphasizing their convergence and feedback regulation, we outline a conceptual framework that integrates multilayered regulation into a cohesive network of stress responses. This synthesis provides a foundation for identifying molecular hubs, testing cross-layer interactions, and developing strategies for engineering As-tolerant crops.