Dicer cleaves double-stranded RNA to yield double-stranded siRNA

Stable Identifier
R-HSA-426464
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Double stranded RNA binds the RISC loading complex and DICER1, an RNase III component of the complex, cleaves double-stranded RNAs to yield short double-stranded RNAs of 21-25 nucleotides, duplex siRNAs (small interfering RNAs). SiRNAs are similar to microRNAs (miRNAs) in their final structure but differ from miRNAs in their source: siRNAs are produced from long double stranded RNAs that originate from viruses, transposable elements, centromeric repeats and other repetitive structures.
The RLC as originally characterized contains DICER1, AGO2, and TARBP2 (TRBP). Alternative RLCs appear to contain other Argonaute proteins (AGO1, AGO3, AGO4) rather than AGO2 and PRKRA rather than TARBP2. Diffusion activity of TARBP2 and PRKRA along duplex RNA may enhance processing by DICER1.

Literature References
PubMed ID Title Journal Year
16357216 A human, ATP-independent, RISC assembly machine fueled by pre-miRNA

Maniataki, E, Mourelatos, Z

Genes Dev 2005
17452327 Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA

Kok, KH, Ng, MH, Ching, YP, Jin, DY

J. Biol. Chem. 2007
16424907 The role of PACT in the RNA silencing pathway

Lee, Y, Hur, I, Park, SY, Kim, YK, Suh, MR, Kim, VN

EMBO J. 2006
23063653 Dicer partner proteins tune the length of mature miRNAs in flies and mammals

Fukunaga, R, Han, BW, Hung, JH, Xu, J, Weng, Z, Zamore, PD

Cell 2012
15973356 TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing

Chendrimada, TP, Gregory, RI, Kumaraswamy, E, Norman, J, Cooch, N, Nishikura, K, Shiekhattar, R

Nature 2005
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
20184375 Recognition of siRNA Asymmetry by TAR RNA Binding Protein

Gredell, JA, Dittmer, MJ, Wu, M, Chan, C, Walton, SP

Biochemistry 2010
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
23658827 Distinguishable in vitro binding mode of monomeric TRBP and dimeric PACT with siRNA

Takahashi, T, Miyakawa, T, Zenno, S, Nishi, K, Tanokura, M, Ui-Tei, K

PLoS ONE 2013
16142218 TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing

Haase, AD, Jaskiewicz, L, Zhang, H, Laine, S, Sack, R, Gatignol, A, Filipowicz, W

EMBO Rep 2005
23251028 ATP-independent diffusion of double-stranded RNA binding proteins

Koh, HR, Kidwell, MA, Ragunathan, K, Doudna, JA, Myong, S

Proc. Natl. Acad. Sci. U.S.A. 2013
12411505 Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP

Zhang, H, Kolb, FA, Brondani, V, Billy, E, Filipowicz, W

EMBO J 2002
12411504 Ribonuclease activity and RNA binding of recombinant human Dicer

Provost, P, Dishart, D, Doucet, J, Frendewey, D, Samuelsson, B, R├ądmark, O

EMBO J 2002
22163034 The role of Dicer protein partners in the processing of microRNA precursors

Koscianska, E, Starega-Roslan, J, Krzyzosiak, WJ

PLoS ONE 2011
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
11201747 Role for a bidentate ribonuclease in the initiation step of RNA interference

Bernstein, E, Caudy, AA, Hammond, SM, Hannon, GJ

Nature 2001
Participants
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Catalyst Activity
Title
ribonuclease III activity of TARBP2,PRKRA RLC [cytosol]
Physical Entity
Activity
Orthologous Events
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