The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Structural insights into RNA processing by the human RISC-loading complex
Open accessAbstract
Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA–generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DE×H/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.
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Cites
Illuminating the silence: understanding the structure and function of small RNAs
Rana, T. M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2085 · Cited by 1,083
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Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462
A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., & Hannon, G. J. (2010) · Nature · doi:10.1038/nature09092 · Cited by 1,149
From guide to target: molecular insights into eukaryotic RNA-interference machinery
Ipsaro, J. J., & Joshua-Tor, L. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2931 · Cited by 281
microRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225
Dicer is dispensable for asymmetric RISC loading in mammals
Betancur, J. G., & Tomari, Y. (2012) · RNA · doi:10.1261/rna.029785.111 · Cited by 84
Functional Interactions Between microRNAs and RNA Binding Proteins
Jiang, P., & Coller, H. (2012) · MicroRNA e · doi:10.2174/2211536611201010070 · Cited by 62
Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB
Jouravleva, K., Golovenko, D., Demo, G., Dutcher, R. C., Hall, T. M. T., Zamore, P. D., & Korostelev, A. A. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.09.002 · Cited by 57
C-terminal tagging impairs AGO2 function
Shah, K. M., Crozier, A. F. F., Assaraf, A., Arya, M., Grevitt, P., Mardakheh, F., Plevin, M. J., & Sharp, T. V. (2025) · RNA Biology · doi:10.1080/15476286.2025.2534028 · Cited by 7
Melet, L., Canan, J., Villalobos, P., Vidal-Veuthey, B., González-Toro, F., Orellana, I., Rivas-Pardo, J. A., Cárdenas, J. P., Moraga, C., Castro-Fernández, V., et al. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.11.009 · Cited by 1
Metadata
- Authors
- Wang, H.-W., Noland, C., Siridechadilok, B., Taylor, D. W., Ma, E., Felderer, K., Doudna, J. A., & Nogales, E.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2009-10-11
- Volume
- 16
- Issue
- 11
- Pages
- 1148-1153
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2051555720
- Cited by
- 255
- References
- 1
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- green
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