Decoding Argonaute specificity: insights from C. elegans and beyond

TABLE 2.

Summary of Argonaute protein PTM

PTM Organism AGO PTM sites Enzyme Effect Citation
Methylation C. elegans CSR-1A RGG/RG motifs (N terminal region) Unknown Promote specificity for spermatogenic 22G-RNAs Nguyen and Phillips 2021
Arabidopsis AGO1 N-terminal region PRMT5 Affects loading of a subset of siRNAs Martín-Merchán et al. 2024
Drosophila Aubergine RA/RG-motifs (N-terminal region) PRMT5 Affects interaction with Tudor domain proteins and piRNA amplification Huang et al. 2021
Phosphorylation C. elegans ALG-1 S988:S998 (PIWI domain) CK1A1 and CK2 Promote efficient AGO-miRISC assembly and target silencing Shah et al. 2023
C. elegans ALG-1 S642 (MID domain) KIN-1 Promote efficient AGO-miRISC assembly and target silencing Quévillon Huberdeau et al. 2022
Human AGO2 S387 (linker region) Akt3 Required for proper P-body localization and translational repression Horman et al. 2013
Human AGO2 Y529 (MID domain) unknown Impairs P-body localization and small RNA association Rüdel et al. 2011
Processing C. elegans WAGO-1, WAGO-3 N terminal region DPF-3 Promote specificity for WAGO-class 22G-RNAs Gudipati et al. 2021
C. elegans ALG-2 N terminal region (in vitro) DPF-3 Regulates ALG-2 protein level Harvey et al. 2025

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  1. RNA 32: 290-310