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
26140367 Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs

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

Mol. Cell 2015
18978028 Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs

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

RNA 2008
15284456 Argonaute2 is the catalytic engine of mammalian RNAi

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

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

Ameres, SL, Martinez, J, Schroeder, R

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

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

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

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

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

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

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

Baillat, D, Shiekhattar, R

Mol Cell Biol 2009
Catalyst Activity

endoribonuclease activity of Endonucleolytic RISC [cytosol]

Orthologous Events
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