Functional analyses of phosphorylation events in human Argonaute 2

Joaquin Lopez-Orozco, Justin M. Pare, Andrea L. Holme, Steven G. Chaulk, Richard P. Fahlman, Tom C. Hobman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Argonaute 2 (Ago2) protein is a central effector of RNA interference (RNAi) pathways and regulates mammalian genes on a global level. The mechanisms of Ago2-mediated silencing are well understood, but less is known about its regulation. Recent reports indicate that phosphorylation significantly affects Ago2 activity. Here, we investigated the effect of mutating all known phospho-residues within Ago2 on its localization and activity. Ago2 associates with two different cytoplasmic RNA granules known as processing bodies (P-bodies) and stress granules, but the nature of this phenomenon is controversial. We report that replacing serine with a phospho-mimetic aspartic acid at position 798 completely abrogates association of Ago2 with P-bodies and stress granules. The effect of this mutation on its activity in gene silencing was modest, which was surprising because association of Ago2 with cytoplasmic RNA granules is thought to be a consequence of its role in RNAi. As such, our data indicate that targeting of Ago2 to P-bodies and stress granules is separable from its role in RNAi and likely requires dynamic phosphorylation of serine 798.

Original languageEnglish
Pages (from-to)2030-2038
Number of pages9
Issue number12
Publication statusPublished - Dec 2015


  • Argonaute
  • P bodies
  • Phosphorylation
  • RNAi
  • Stress granules


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