Endonucleolytic RISC hydrolyzes target RNAs

Stable Identifier
Reaction [transition]
Homo sapiens
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Human Argonaute-2 (AGO2, EIF2C2) possesses ribonucleolytic activity in its PIWI domain and cleaves target RNAs that are exactly complementary to the guide RNA at a location around 10 nucleotides from the 5' end of the match with the guide RNA. The products of cleavage have a 5' phosphate and a 3' hydroxyl group. Both complexes containing siRNAs and miRNAs are capable of cleavage. Although Argonaute proteins interact with many other proteins, the complex of AGO2 and the guide RNA are sufficient to direct cleavage of target RNAs in vitro. In vivo, cleavage requires interaction of AGO2 with a TNRC6 protein and MOV10.
Literature References
PubMed ID Title Journal Year
18978028 Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs

Ojo, T, Landthaler, M, Hafner, M, Tuschl, T, Soll, SJ, Zavolan, M, Gaidatzis, D, Dinic, L, Rothballer, A, Chen, PY

RNA 2008
26140367 Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs

Hohng, S, Jung, SR, Jo, MH, Shin, S, Song, JJ, Kim, E

Mol. Cell 2015
15284456 Argonaute2 is the catalytic engine of mammalian RNAi

Hammond, SM, Marsden, CG, Liu, J, Carmell, MA, Hannon, GJ, Song, JJ, Thomson, JM, Rivas, FV, Joshua-Tor, L

Science 2004
17632058 Molecular basis for target RNA recognition and cleavage by human RISC

Schroeder, R, Ameres, SL, Martinez, J

Cell 2007
15260970 Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs

Teng, G, Landthaler, M, Tuschl, T, Patkaniowska, A, Dorsett, Y, Meister, G

Mol Cell 2004
15800637 Purified Argonaute2 and an siRNA form recombinant human RISC

Liu, J, Hannon, GJ, Song, JJ, Rivas, FV, Aragon, JP, Tolia, NH, Joshua-Tor, L

Nat Struct Mol Biol 2005
16289642 Identification of novel argonaute-associated proteins

Urlaub, H, Landthaler, M, L├╝hrmann, R, Tuschl, T, Peters, L, Chen, PY, Meister, G

Curr Biol 2005
12154197 A microRNA in a multiple-turnover RNAi enzyme complex

Hutvagner, G, Zamore, PD

Science 2002
19470757 Functional Dissection of Human TNRC6, GW182-related, Family of proteins

Shiekhattar, R, Baillat, D

Mol Cell Biol 2009
Catalyst Activity

RNA endonuclease activity of Endonucleolytic RISC [cytosol]

Orthologous Events
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