| Structural highlights
Function
[AGO1_HUMAN] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).[1] [2] [3] [TNR6A_HUMAN] Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As scaffoldng protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes.[4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
In miRNA-mediated gene silencing, the physical interaction between human Argonaute (hAgo) and GW182 (hGW182) is essential for facilitating the downstream silencing of the targeted mRNA. GW182 can interact with hAgo via three of the GW/WG repeats in its Argonaute-binding domain: motif-1, motif-2, and the hook motif. The structure of hAgo1 in complex with the hook motif of hGW182 reveals a "gate"-like interaction that is critical for GW182 docking into one of hAgo1's tryptophan-binding pockets. We show that hAgo1 and hAgo2 have a single GW182-binding site and that miRNA binding increases hAgo's affinity to GW182. With target binding occurring rapidly, this ensures that only mature RISC would be recruited for silencing. Finally, we show that hGW182 can recruit up to three copies of hAgo via its three GW motifs. This may explain the observed cooperativity in miRNA-mediated gene silencing.
Multivalent Recruitment of Human Argonaute by GW182.,Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, Tuschl T. Identification of novel argonaute-associated proteins. Curr Biol. 2005 Dec 6;15(23):2149-55. Epub 2005 Nov 10. PMID:16289642 doi:10.1016/j.cub.2005.10.048
- ↑ Janowski BA, Huffman KE, Schwartz JC, Ram R, Nordsell R, Shames DS, Minna JD, Corey DR. Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nat Struct Mol Biol. 2006 Sep;13(9):787-92. Epub 2006 Aug 27. PMID:16936728 doi:nsmb1140
- ↑ Wu L, Fan J, Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. 2008 Sep 9;18(17):1327-32. doi: 10.1016/j.cub.2008.07.072. PMID:18771919 doi:10.1016/j.cub.2008.07.072
- ↑ Jakymiw A, Lian S, Eystathioy T, Li S, Satoh M, Hamel JC, Fritzler MJ, Chan EK. Disruption of GW bodies impairs mammalian RNA interference. Nat Cell Biol. 2005 Dec;7(12):1267-74. Epub 2005 Nov 13. PMID:16284622 doi:http://dx.doi.org/10.1038/ncb1334
- ↑ Liu J, Rivas FV, Wohlschlegel J, Yates JR 3rd, Parker R, Hannon GJ. A role for the P-body component GW182 in microRNA function. Nat Cell Biol. 2005 Dec;7(12):1261-6. Epub 2005 Nov 13. PMID:16284623 doi:http://dx.doi.org/ncb1333
- ↑ Lian S, Fritzler MJ, Katz J, Hamazaki T, Terada N, Satoh M, Chan EK. Small interfering RNA-mediated silencing induces target-dependent assembly of GW/P bodies. Mol Biol Cell. 2007 Sep;18(9):3375-87. Epub 2007 Jun 27. PMID:17596515 doi:http://dx.doi.org/E07-01-0070
- ↑ Wakiyama M, Takimoto K, Ohara O, Yokoyama S. Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system. Genes Dev. 2007 Aug 1;21(15):1857-62. PMID:17671087 doi:http://dx.doi.org/10.1101/gad.1566707
- ↑ Li S, Lian SL, Moser JJ, Fritzler ML, Fritzler MJ, Satoh M, Chan EK. Identification of GW182 and its novel isoform TNGW1 as translational repressors in Ago2-mediated silencing. J Cell Sci. 2008 Dec 15;121(Pt 24):4134-44. PMID:19056672 doi:http://dx.doi.org/121/24/4134
- ↑ Zipprich JT, Bhattacharyya S, Mathys H, Filipowicz W. Importance of the C-terminal domain of the human GW182 protein TNRC6C for translational repression. RNA. 2009 May;15(5):781-93. Epub 2009 Mar 20. PMID:19304925 doi:rna.1448009
- ↑ Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L. Multivalent Recruitment of Human Argonaute by GW182. Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232 doi:http://dx.doi.org/10.1016/j.molcel.2017.07.007
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