Reactome | RISC binds inexactly matching target RNAs

RISC binds inexactly matching target RNAs

Stable Identifier

R-HSA-426489

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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RISC binds inexactly matching target RNAs

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RISCs can bind target RNAs that do not exactly match the guide RNA carried by an Argonaute. Binding is especially dependent on base-pairing between the target RNA and the eight 5' nucleotides of the guide RNA (miRNA or siRNA). After binding, Argonaute-1 (AGO1, EIF2C1), AGO3 (EIF2C3), and AGO4 (EIF2C4) are incapable of cleavage in all cases. AGO2 is capable of cleaving the target RNA but not if mismatches exist in the middle of the guide (centered about 10 nucloetides from the 5' end of the guide RNA). In the absence of cleavage the target RNA remains bound by the RISC, which inhibits translation of the target RNA and causes the RNA to enter the decay pathway. In vivo, inhibition of translation requires interaction of AGO with a TNRC6 protein and MOV10. The phosphoinositide-3 kinase/mTOR pathway increases expression of GW182, a TNRC6 protein, which increases the portion of AGO:miRNA in high molecular weight complexes with mRNA.

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
24043833	Structural features of Argonaute-GW182 protein interactions Pfaff, J, Hennig, J, Herzog, F, Aebersold, R, Sattler, M, Niessing, D, Meister, G	Proc. Natl. Acad. Sci. U.S.A.	2013
19383768	The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins Lazzaretti, D, Tournier, I, Izaurralde, E	RNA	2009
18461144	Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance Hendrickson, DG, Hogan, DJ, Herschlag, D, Ferrell, JE, Brown, PO	PLoS One	2008
16289642	Identification of novel argonaute-associated proteins Meister, G, Landthaler, M, Peters, L, Chen, PY, Urlaub, H, Lührmann, R, Tuschl, T	Curr Biol	2005
19470757	Functional Dissection of Human TNRC6, GW182-related, Family of proteins Baillat, D, Shiekhattar, R	Mol Cell Biol	2009
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
16284623	A role for the P-body component GW182 in microRNA function Liu, J, Rivas, FV, Wohlschlegel, J, Yates, JR 3rd, Parker, R, Hannon, GJ	Nat Cell Biol	2005
17632058	Molecular basis for target RNA recognition and cleavage by human RISC Ameres, SL, Martinez, J, Schroeder, R	Cell	2007
28781232	Multivalent Recruitment of Human Argonaute by GW182 Elkayam, E, Faehnle, CR, Morales, M, Sun, J, Li, H, Joshua-Tor, L	Mol. Cell	2017
25359968	Structural basis for microRNA targeting Schirle, NT, Sheu-Gruttadauria, J, MacRae, IJ	Science	2014
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
19398495	Mammalian GW182 contains multiple Argonaute-binding sites and functions in microRNA-mediated translational repression Takimoto, K, Wakiyama, M, Yokoyama, S	RNA	2009
17128271	Evidence that microRNAs are associated with translating messenger RNAs in human cells Maroney, PA, Yu, Y, Fisher, J, Nilsen, TW	Nat Struct Mol Biol	2006
15014042	Specificity of microRNA target selection in translational repression Doench, JG, Sharp, PA	Genes Dev	2004