Salinity stress is a major abiotic constraint to rice cultivation, limiting growth and yield worldwide. Autophagy, a conserved recycling pathway, and microRNAs (miRNAs), key post-transcriptional regulators, are emerging as central players in stress adaptation, yet their integrated roles in salinity tolerance remain unclear. Here, we compared physiological, biochemical, and molecular responses of two salt-sensitive (IR64, BPT5204) and two salt-tolerant (CSR23, Luna Sankhi) rice varieties under salinity stress. Sensitive varieties showed growth inhibition, oxidative damage, and ion imbalance, whereas tolerant varieties maintained stronger antioxidant activity, selective K⁺ uptake, and osmolyte accumulation. Microscopy and gene expression analyses revealed earlier and stronger autophagy induction in sensitive lines, with differential regulation of ATG5, ATG8d, and ATG12 genes. Heterologous expression of these genes in E. coli enhanced tolerance to salt and osmotic stress, suggesting possible non-canonical roles. Small RNA sequencing indicated salt-stress led upregulation of miRNAs in sensitive varieties targeting autophagy, ion transport, redox balance, and growth pathways. qRT-PCR validation identified osa-miR1432-5p, osa-miR-1861e, and osa-miR-1874-3p as key regulators of autophagy, redox balance, and ionic homeostasis in contrasting genotypes. Notably, osa-miR1432-5p is predicted to target TOR (Target of Rapamycin), a master autophagy regulator, providing a potential direct link between miRNA control and autophagy activation in salt-sensitive rice. These regulatory modules, together with physiological and transcriptional adjustments, distinguish the proactive tolerance of CSR and LS from the reactive stress response of IR and BPT. GO enrichment analysis revealed that BPT suppresses growth and metabolic pathways under salinity, while CSR sustains redox regulation, peroxisomal function, and ion transport, conferring superior stress tolerance. Together, these findings demonstrate that autophagy and miRNA-mediated regulation shape contrasting salinity responses in rice. Tolerant varieties appear to adopt more proactive adaptive responses, while sensitive varieties rely on rapid but costly induction of autophagy and miRNAs. These insights highlight autophagy–miRNA interactions as a potential target for engineering salt-resilient rice.
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