The multifaceted regulatory network of microRNA396: Orchestrating plant plasticity through coordinating development and various stresses

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression in eukaryotes. Among them, miR396 targets GROWTH-REGULATING FACTOR (GRF) transcription factors and forms one of the most highly conserved regulatory modules in plants. Recent studies have greatly expanded the functional landscape of the miR396-GRF module, showing that, beyond its canonical role in leaf morphogenesis, it also participates in root meristem regulation, reproductive development, yield formation, tissue regeneration, and responses to diverse abiotic and biotic stresses. In crop plants, this module further controls agronomically important traits. Here, we summarize current knowledge of the evolutionary conservation and diversification of the MIR396 loci, the upstream pathways that control miR396 expression, and the developmental and stress-related outputs mediated by the miR396-GRF module. We also discuss evidence that miR396 functions as a context-dependent regulator rather than a simple growth suppressor, and highlight how precise manipulation of the miR396-GRF module may provide new opportunities for crop improvement by optimizing growth, regeneration, and stress resilience.