ARGONAUTE (AGO) proteins in plants are pivotal regulators of gene expression through small RNA-guided mechanisms. All AGOs share the same domain organization, consisting of four highly conserved domains: N, PAZ, MID, and PIWI. Besides, AGOs possess an unstructured amino-terminal extension (NTE). Recent studies have revealed that plants’ NTEs exhibit variable lengths and sequences, with a strong correlation among AGOs from the same clade which share similar functions. This variability, observed across different AGOs and clades, suggests a potential link between the NTE’s characteristics and the functional roles of AGOs (Martín-Merchán et al J. Exp. Bot. 2023).
Among the ten AGOs in Arabidopsis thaliana, AGO1 stands out as the main effector of post-transcriptional gene silencing. Intriguingly, the NTE of AGO1, has gained prominence in recent studies linked to diverse regulatory functions, including subcellular localization, sRNA loading, and interactions with regulatory factors. Here, we have elucidated that NTEAGO1 undergoes symmetric arginine dimethylation on specific residues, and interacts with the methyltransferase PRMT5, which catalyzes its methylation. Notably, we observed that the lack of symmetric dimethylarginine has no discernible impact on its subcellular localization or miRNA loading capabilities. However, the absence of PRMT5 significantly alters the loading of a subgroup of sRNAs into AGO1 and reshapes the NTEAGO1 interactome. Importantly, our research extends beyond AGO1, illustrating that symmetric arginine dimethylation of NTEs is a common process across At-AGOs, taking place in AGO1, AGO2, AGO3 and AGO5, deepening our understanding of PTMs in the intricate landscape of RNA-associated gene regulation (Martín-Merchán et al under revision).