Dicer cleaves pre-miRNA to yield duplex miRNA

Stable Identifier
R-HSA-203862
Type
Reaction [transition]
Species
Homo sapiens
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Pre-miRNA binds the RISC loading complex (RLC), a complex containing DICER1, AGO2, and TARBP2 (TRBP). Alternative loading complexes contain AGO1, AGO3, or AGO4 rather than AGO2 and PRKRA (PACT) rather than TARBP2. The pre-miRNA substrate has an internal loop and a protruding 3' end created by cleavage by DROSHA:DGCR8. The DICER1:TARBP2 subcomplex or DICER1:PRKRA subcomplex recognizes this structure and the DICER1 component cleaves the pre-miRNA near the loop. The product is a double-stranded RNA of 21-25 nucleotides having 2-nucleotide protrusions at each 3' end. The products have 5' phosphates and 3' hydroxyl groups. 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
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
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
23624860 Substrate-specific structural rearrangements of human Dicer

Taylor, DW, Ma, E, Shigematsu, H, Cianfrocco, MA, Noland, CL, Nagayama, K, Nogales, E, Doudna, JA, Wang, HW

Nat. Struct. Mol. Biol. 2013
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
11452083 A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA

Hutvagner, G, McLachlan, J, Pasquinelli, AE, Balint, E, Tuschl, T, Zamore, PD

Science 2001
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
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Catalyst Activity
Title
ribonuclease III activity of TARBP2,PRKRA RLC [cytosol]
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