Soybean nodules offer an ideal system for dissecting RNA-mediated regulation of symbiosis. Through dual RNA-seq and small RNA profiling from 2–10 weeks post-inoculation, we identified three distinct nodule developmental phases: early development, active nitrogen fixation, and senescence (DelPercio et al. 2025). We demonstrated that soybeans undergo extensive transcriptional reprogramming during senescence, whereas Bradyrhizobium exhibits its major transcriptional shifts earlier, during nodule establishment. We identified soybean lipoxygenases and specific microRNAs (such as miR397 and miR171) as candidate biomarkers of nitrogen fixation and nodule aging, and uncovered the upregulation of Bradyrhizobium stress-response genes (e.g., paa operon, rpoH) that enable bacterial survival beyond symbiosis. This work provided new molecular markers and regulatory frameworks for improving the efficiency and longevity of symbiotic nitrogen fixation.