Argonaute

    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 small interfering RNA (siRNA) fragments and have endonuclease activity directed against messenger RNA (mRNA) strands that are complementary to their bound siRNA fragment. The proteins are also partially responsible for selection of the guide strand and destruction of the passenger strand of the siRNA substrate.^[1]

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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.^[2]

In eukaryotes, argonaute proteins have been identified in high concentrations in regions of the cell's cytoplasm known as cytoplasmic bodies, to which mRNA decay is also localized.^[3] 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.^[4]

Argonaute proteins are named after the argonaute (AGO) phenotype of Arabidopsis mutants, which itself was named after its resemblance to argonauts. ^[5]

References

1. ^ Rand TA, Petersen S, Du F, Wang X. (2005). Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123(4):621-9.
2. ^ Ma J, Yuan Y, Meister G, Pei Y, Tuschl T, Patel D (2005). "Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein". Nature 434 (7033): 666-70. PMID 15800629.
3. ^ Sen GL, Blau HM. (2005). Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 7(6):633-6.
4. ^ Anantharaman V, Koonin E, Aravind L (2002). "Comparative genomics and evolution of proteins involved in RNA metabolism". Nucleic Acids Res 30 (7): 1427-64. PMID 11917006.
5. ^ Bohmert et al. (1998). AGO1 defines a novel locus of Arabidopsis controlling leaf development. The EMBO Journal 17, 170–180, PubMed