Unlike most other land plants, legumes can fulfill their nitrogen needs through the establishment of symbioses with nitrogen-fixing soil bacteria (rhizobia). Through this symbiosis, fixed nitrogen is incorporated into the food chain. Because of this ecological relevance, the genetic mechanisms underlying the establishment of the legume–rhizobia symbiosis (LRS) have been extensively studied over the past decades. During this time, different types of regulators of this symbiosis have been discovered and characterized. A growing number of studies have demonstrated the participation of different types of small RNAs, including microRNAs, in the different stages of this symbiosis. The involvement of small RNAs also indicates that Argonaute (AGO) proteins participate in the regulation of the LRS. However, despite this obvious role, the relevance of AGO proteins in the LRS has been overlooked and understudied. Here, we discuss and hypothesize the likely participation of AGO proteins in the regulation of the different steps that enable the establishment of the LRS. We also briefly review and discuss whether rhizobial symbiosis induces DNA damages in the legume host. Understanding the different levels of LRS regulation could lead to the development of improved nitrogen fixation efficiency to enhance sustainable agriculture, thereby reducing dependence on inorganic fertilizers.Fil: Valdés-López, Oswaldo. Universidad Nacional Autónoma de México, Escuela Nacional de Estudios Profesionales Iztacala; MéxicoFil: Formey, Damien. Universidad Nacional Autónoma de México; MéxicoFil: Isidra-Arellano, Mariel C.. Universidad Nacional Autónoma de México, Escuela Nacional de Estudios Profesionales Iztacala; México. Universidad Nacional Autónoma de México; MéxicoFil: Reyero-Saavedra, Maria del Rocio. Universidad Nacional Autónoma de México, Escuela Nacional de Estudios Profesionales Iztacala; MéxicoFil: Fernandez Göbel, Tadeo Francisco. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires; Argentina. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigaciones Agropecuarias. Unidad de Estudios Agropecuarios. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Unidad de Estudios Agropecuarios.; ArgentinaFil: Sánchez-Correa, Maria del Socorro. Universidad Nacional Autónoma de México, Escuela Nacional de Estudios Profesionales Iztacala; Méxic
