Removal of siRNA passenger strand

Stable Identifier
Reaction [omitted]
Homo sapiens
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The short double-stranded RNA passed from DICER1 to an Argonaute protein is rendered single-stranded by removal and loss of the passenger strand through a mechanism that is not well characterized. All Argonautes (AGO1 (EIF2C1), AGO2 (EIF2C2), AGO3 (EIF2C3), AGO4 (EIF2C4)) can remove the passenger strand without cleaving it. AGO2 (EIF2C2) possesses endonucleolytic activity and cleaves the passenger strand of siRNAs, which facilitates removal of the passenger strand but is not required (Matranga et al. 2005). RNA helicase A associated with the RISC loading complex can also facilitate removal of the passenger strand.
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.
Argonaute proteins loaded with miRNAs or siRNAs are predominantly located in association with TARBP2 or PRKRA at the cytosolic face of the rough endoplasmic reticulum in cultured cells.
Literature References
PubMed ID Title Journal Year
23511973 The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing

Hean, J, Aeschimann, F, Basselet, P, Stalder, L, Hintersteiner, M, Heusermann, W, Meisner-Kober, NC, Wirz, J, Morrissey, DV, Sokol, L, Pfanzagl, V, Trojer, D, Fritzsche, A, Weiler, J

EMBO J. 2013
17531811 RNA helicase A interacts with RISC in human cells and functions in RISC loading

Rana, TM, Robb, GB

Mol Cell 2007
22106413 Dicer is dispensable for asymmetric RISC loading in mammals

Betancur, JG, Tomari, Y

RNA 2012
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
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
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
23661684 Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing

Zhou, K, Doudna, JA, Noland, CL, Smith, AM, Lee, HY

Nucleic Acids Res. 2013
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
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