Ubiquitination as a multi-layer regulatory network in legume-rhizobium symbiosis.

Symbiotic nitrogen fixation (SNF) by legumes is essential for sustainable agriculture, providing plant-available nitrogen while reducing reliance on synthetic fertilizers. The establishment of legume-rhizobium symbiosis requires tightly regulated host signaling to coordinate rhizobia infection, nodule development, and nitrogen fixation, while preventing excessive colonization or immune activation. Accumulating evidence indicates that ubiquitination, mediated by E1, E2, E3 ubiquitin ligases and deubiquitinating enzymes, plays a central role in controlling multiple stages of this process. In this review, we summarize current knowledge on ubiquitination-mediated regulation of symbiotic nitrogen fixation, with a focus on early symbiotic signaling and nodule development. We highlight key E3 ligases that modulate Nod factor receptor homeostasis, receptor-associated kinases, transcription factors, and infection thread growth, and discuss how ubiquitination interfaces with nutrient and stress signaling pathways. Finally, we outline key knowledge gaps and discuss the potential of manipulating ubiquitination pathways to improve nodulation efficiency and nitrogen use efficiency in crops.