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).[1] Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs) [2]. 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 [3]. These proteins are also partially responsible for selection of the guide strand and destruction of the passenger strand of the siRNA substrate.[4]
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.[5]
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.[6][7] 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).[8]
Argonaute proteins are named after the argonaute (AGO) phenotype of Arabidopsis thaliana mutants, which itself was named after its resemblance to argonauts. [9]
HITS-CLIP (High-thoughput sequencing of cross-linking immunoprecipitation) of Argonaute has been used as a method to identifying microRNA targets [10], since in these experiments the microRNAs bound to Argonaute as well as their mRNA targets will be immunoprecipitated and sequenced.
[edit] References
- ^ Cenik ES, Zamore PD. (2011). "Argonaute proteins.". Current Biology 21 (12): R446–9. doi:10.1016/j.cub.2011.05.020. PMID 21683893.
- ^ Ghildiyal M, Zamore PD (2009). "Small silencing RNAs: an expanding universe". Nat. Rev. Genet 10 (2): 94–108. doi:10.1038/nrg2504. PMC 2724769. PMID 19148191. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2724769.
- ^ Tolia, N. H. & Joshua-Tor, L. Slicer and the argonautes. Nature Chem. Biol. 3, 36–43 (2007).
- ^ 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. doi:10.1016/j.cell.2005.10.020. PMID 16271385.
- ^ 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. doi:10.1038/nature03514. PMID 15800629.
- ^ Parker R., Sheth U. (2007). "P bodies and the control of mRNA translation and degradation". Mol. Cell 25 (5): 635–646. doi:10.1016/j.molcel.2007.02.011. PMID 17349952.
- ^ 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. doi:10.1038/ncb1265. PMID 15908945.
- ^ Anantharaman V, Koonin E, Aravind L (2002). "Comparative genomics and evolution of proteins involved in RNA metabolism". Nucleic Acids Res 30 (7): 1427–64. doi:10.1093/nar/30.7.1427. PMC 101826. PMID 11917006. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=101826.
- ^ Bohmert et al. (1998). AGO1 defines a novel locus of Arabidopsis controlling leaf development. The EMBO Journal 17, 170–180, PubMed
- ^ Thomson, DW; Bracken, CP, Goodall, GJ (2011 Jun 7). "Experimental strategies for microRNA target identification". Nucleic Acids Research 39 (16): 6845–53. doi:10.1093/nar/gkr330. PMC 3167600. PMID 21652644. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3167600.
[edit] External links
- starBase database: a database for exploring microRNA–mRNA interaction maps from Argonaute CLIP-Seq(HITS-CLIP, PAR-CLIP) and Degradome-Seq data.
