|Argonaute Piwi domain|
|Argonaute Paz domain|
Argonaute proteins are the catalytic components of the RNA-induced silencing complex (RISC), the protein complex responsible for the gene silencing phenomenon known as RNA interference (RNAi). Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity, which typically leads to silencing of the target. Some of the Argonaute proteins have endonuclease activity directed against messenger RNA (mRNA) strands that display extensive complementarity to their bound small RNA, and this is known as Slicer activity. These proteins are also partially responsible for selection of the guide strand and destruction of the passenger strand of the siRNA substrate.
The structural basis for binding of RNA to the Argonaute protein has been examined by X-ray crystallography of the binding domain of an RNA-bound argonaute protein. The phosphorylated 5' end of the RNA strand enters a conserved basic surface pocket and makes contacts through a divalent cation such as magnesium and by aromatic stacking between the 5' nucleotide in the siRNA and a conserved tyrosine residue. This site is thought to form a nucleation site for the binding of the siRNA to its mRNA target.
In Eukaryotes, Argonaute proteins have been identified in high concentrations in regions of the cell's cytoplasm known as processing bodies (P-bodies), to which enzymes that participate in mRNA decay pathways are also localized. The Argonaute protein family is shared among not only eukaryotes, but also archaea and certain bacteria such as Aquifex aeolicus. Based on comparative genomics studies, the argonaute family is thought to have evolved from components of the translation initiation system, due to their homology to eukaryotic Initiation Factor 2 (eIF2).
HITS-CLIP (high-thoughput sequencing of cross-linking immunoprecipitation) of Argonaute has been used as a method to identifying microRNA targets, since in these experiments the microRNAs bound to Argonaute as well as their mRNA targets will be immunoprecipitated and sequenced.
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