Removal of miRNA passenger strand

Stable Identifier
Reaction [omitted]
Homo sapiens
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A short double-stranded RNA is passed from DICER1 to an Argonaute protein and rendered single-stranded by removal and loss of the passenger strand. All Argonautes (AGO1 (EIF2C1), AGO2 (EIF2C2), AGO3 (EIF2C3), AGO4 (EIF2C4)) can remove the passenger strand without cleaving it and most miRNAs are processed in this way. AGO2 (EIF2C2) can cleave the passenger strand of a subset of miRNAs that have no mismatches in the central region (Shin et al. 2008).
RNA helicase A associated with the RISC loading complex can 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.
In cultured cells 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 adult non-dividing cells most Argonaute-bound miRNAs are located in low molecular weight complexes but shift to larger complexes containing GW182 in response to phosphoinositide-3-kinase/mTOR signaling.
Literature References
PubMed ID Title Journal Year
18728384 Cleavage of the star strand facilitates assembly of some microRNAs into Ago2-containing silencing complexes in mammals

Shin, C

Mol Cells 2008
16357216 A human, ATP-independent, RISC assembly machine fueled by pre-miRNA

Mourelatos, Z, Maniataki, E

Genes Dev 2005
23531496 Multiple sensors ensure guide strand selection in human RNAi pathways

Doudna, JA, Noland, CL

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

Rana, TM, Robb, GB

Mol Cell 2007
25568082 In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA

Vidigal, JA, Ventura, A, Briskin, D, Leslie, CS, DeMatteo, RG, Lindsten, T, Thompson, CB, La Rocca, G, Radler, MR, Olejniczak, SH, González, AJ, Tuschl, T, Spraggon, L

Proc. Natl. Acad. Sci. U.S.A. 2015
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
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
18178619 In vitro reconstitution of the human RISC-loading complex

Ma, E, Zhou, M, Robinson, CV, Doudna, JA, MacRae, IJ

Proc Natl Acad Sci U S A 2008
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