AGO2 cleaves passenger strand of duplex siRNA

Stable Identifier
Reaction [transition]
Homo sapiens
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C3PO appears to act as a nuclease that hydrolyzes the passenger strand after cleavage by AGO2. C3PO could also be part of a DICER1-independent pathway for loading AGO2. AGO2 of humans may contain either miRNAs or siRNAs.
The mechanism that selects which strand is retained as the guide RNA is not well understood in humans. Overhanging nucleotides and strength of base-pairing at each end of the input duplex are observed to influence strand selection.
Literature References
PubMed ID Title Journal Year
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
18842624 Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells

Schwille, P, Mütze, J, Crell, K, Weinmann, L, Staroske, W, Höck, J, Ohrt, T, Meister, G

Nucleic Acids Res 2008
22106413 Dicer is dispensable for asymmetric RISC loading in mammals

Betancur, JG, Tomari, Y

RNA 2012
17531811 RNA helicase A interacts with RISC in human cells and functions in RISC loading

Rana, TM, Robb, GB

Mol Cell 2007
19966796 ATP-dependent human RISC assembly pathways

Kawamata, T, Iwasaki, S, Ye, X, Paroo, Z, Tomari, Y, Yoda, M, Liu, Q

Nat Struct Mol Biol 2010
16271386 Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes

Matranga, C, Tomari, Y, Zamore, PD, Bartel, DP, Shin, C

Cell 2005
21552258 Structure of C3PO and mechanism of human RISC activation

Liu, Y, Zhang, H, Huang, N, Ye, X, Liu, Q, Chen, S, Paroo, Z, Li, P, Huerta, C

Nat. Struct. Mol. Biol. 2011
18782830 Effect of asymmetric terminal structures of short RNA duplexes on the RNA interference activity and strand selection

Takagi, Y, Sano, M, Nakanishi, M, Miyagishi, M, Sutou, S, Sierant, M

Nucleic Acids Res 2008
17932509 Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells

Urlaub, H, Rüdel, S, Ender, C, Weinmann, L, Höck, J, Raabe, M, Meister, G, Kremmer, E

EMBO Rep 2007
19401777 Both strands of siRNA have potential to guide posttranscriptional gene silencing in mammalian cells

Sun, JF, Zhang, Y, Jia, LT, Meng, YL, Yang, AG, Yao, LB, Li, X, Zhang, HZ, Yang, J, Wei, JX

PLoS One 2009
Catalyst Activity

endoribonuclease activity of AGO2:duplex siRNA [cytosol]

Orthologous Events
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