%0 Journal Article
%T Posttranslational modification of Argonautes and their role in small RNA-mediated gene regulation
%A Michael Johnston
%A Gyorgy Hutvagner
%J Silence
%D 2011
%I BioMed Central
%R 10.1186/1758-907x-2-5
%X Small RNA such as miRNA and siRNA have emerged as important eukaryotic posttranscriptional gene regulators. Functioning as guides, these small RNA direct Argonaute proteins to complementary targeted mRNA, often resulting in reduced gene expression by a variety of mechanisms [1-3]. Since the discovery of small RNAs, much focus has been directed toward dissecting their mode of action. Very recently, an increasing number of studies have also started to reveal mechanisms for the turnover of miRNAs [4,5]. However, the mechanisms that mediate the stability and activity of the pathways' central protein components, Argonautes, are less understood and are the topic of this review. We summarise studies that have identified posttranslational modifications of Argonaute and Piwi proteins and how these modifications affect Argonautes' function and/or turnover. We also reflect on the potential wider biological implications of these posttranslational modifications on gene silencing by modulating Argonautes' activity and/or turnover.Studies of a variety of organisms have shown that deletion or overexpression of the enzymes involved in miRNA biogenesis and action can severely disrupt major cellular process. Therefore, it is a cellular necessity to maintain the homeostasis of these components, which can be dynamically regulated in response to internal or external stimuli. An elegant example of this is a negative feedback loop that exists in Arabidopsis. Where AGO1, the main Argonaute directing miRNA and siRNA silencing in plants, is involved in a posttranscriptional autoregulatory loop with a low-abundance miRNA, miR168 [6]. Only when AGO1 protein levels increase is miR168 able to incorporate into the RNA-induced silencing complex (RISC) efficiently and target AGO1 mRNA. The inverse is also true. When AGO1 protein levels decrease, miR168 is less effectively loaded into RISC and a consequent AGO1 mRNA increase is observed; thus small perturbations are compensated for to maintain AGO1 e
%K posttranslational modifications
%K phosphorylation
%K ubiquitination
%K Argonautes
%K miRNA
%K RNAi
%U http://www.silencejournal.com/content/2/1/5