Reactome | Removal of miRNA passenger strand

Removal of miRNA passenger strand

Stable Identifier

R-HSA-210805

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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 Maniataki, E, Mourelatos, Z	Genes Dev	2005
23531496	Multiple sensors ensure guide strand selection in human RNAi pathways Noland, CL, Doudna, JA	RNA	2013
23661684	Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing Lee, HY, Zhou, K, Smith, AM, Noland, CL, Doudna, JA	Nucleic Acids Res.	2013
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
23511973	The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing Stalder, L, Heusermann, W, Sokol, L, Trojer, D, Wirz, J, Hean, J, Fritzsche, A, Aeschimann, F, Pfanzagl, V, Basselet, P, Weiler, J, Hintersteiner, M, Morrissey, DV, Meisner-Kober, NC	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 Ohrt, T, Mütze, J, Staroske, W, Weinmann, L, Höck, J, Crell, K, Meister, G, Schwille, P	Nucleic Acids Res	2008
17531811	RNA helicase A interacts with RISC in human cells and functions in RISC loading Robb, GB, Rana, TM	Mol Cell	2007
25568082	In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA La Rocca, G, Olejniczak, SH, González, AJ, Briskin, D, Vidigal, JA, Spraggon, L, DeMatteo, RG, Radler, MR, Lindsten, T, Ventura, A, Tuschl, T, Leslie, CS, Thompson, CB	Proc. Natl. Acad. Sci. U.S.A.	2015
19966796	ATP-dependent human RISC assembly pathways Yoda, M, Kawamata, T, Paroo, Z, Ye, X, Iwasaki, S, Liu, Q, Tomari, Y	Nat Struct Mol Biol	2010
16271386	Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes Matranga, C, Tomari, Y, Shin, C, Bartel, DP, Zamore, PD	Cell	2005
18782830	Effect of asymmetric terminal structures of short RNA duplexes on the RNA interference activity and strand selection Sano, M, Sierant, M, Miyagishi, M, Nakanishi, M, Takagi, Y, Sutou, S	Nucleic Acids Res	2008
17932509	Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells Höck, J, Weinmann, L, Ender, C, Rüdel, S, Kremmer, E, Raabe, M, Urlaub, H, Meister, G	EMBO Rep	2007
19401777	Both strands of siRNA have potential to guide posttranscriptional gene silencing in mammalian cells Wei, JX, Yang, J, Sun, JF, Jia, LT, Zhang, Y, Zhang, HZ, Li, X, Meng, YL, Yao, LB, Yang, AG	PLoS One	2009
18178619	In vitro reconstitution of the human RISC-loading complex MacRae, IJ, Ma, E, Zhou, M, Robinson, CV, Doudna, JA	Proc Natl Acad Sci U S A	2008