Human Argonaute 2 Has diverse reaction pathways on Target RNAs
Open accessAbstract
Argonaute is a key enzyme of various RNA silencing pathways. We use single-molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs).
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The degree of MRE complementarity determines whether there is AGO2-dependent slicing of target mRNA or miRISC-mediated translational inhibition and target mRNA decay.
“The degree of MRE complementarity determines whether there is AGO2-dependent slicing of target mRNA or miRISC-mediated translational inhibition and target mRNA decay (47).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [47]
Cites
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993) · Cell · doi:10.1016/0092-8674(93)90529-y · Cited by 12,948 · see citing works
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855 · see citing works
Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
Lim, L. P., Lau, N. C., Garrett-Engele, P., Grimson, A., Schelter, J. M., Castle, J., Bartel, D. P., Linsley, P. S., & Johnson, J. M. (2005) · Nature · doi:10.1038/nature03315 · Cited by 4,755 · see citing works
Wightman, B., Ha, I., & Ruvkun, G. (1993) · Cell · doi:10.1016/0092-8674(93)90530-4 · Cited by 4,292 · see citing works
RNA interference is mediated by 21- and 22-nucleotide RNAsPreprint
Elbashir, S. M., Lendeckel, W., & Tuschl, T. (2001) · Genes & Development · doi:10.1101/gad.862301 · Cited by 3,310 · see citing works
A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
Hamilton, A. J., & Baulcombe, D. C. (1999) · Science · doi:10.1126/science.286.5441.950 · Cited by 3,048 · see citing works
An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells
Hammond, S. M., Bernstein, E., Beach, D., & Hannon, G. J. (2000) · Nature · doi:10.1038/35005107 · Cited by 3,006 · see citing works
Argonaute2 is the catalytic engine of mammalian RNAi
Liu, J., Carmell, M. A., Rivas, F. V., Marsden, C. G., Thomson, J. M., Song, J.-J., Hammond, S. M., Joshua-Tor, L., & Hannon, G. J. (2004) · Science · doi:10.1126/science.1102513 · Cited by 2,353 · see citing works
Self-citationGene silencing by microRNAs: contributions of translational repression and mRNA decay
Huntzinger, E., & Izaurralde, E. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2936 · Cited by 2,339 · see citing works
A practical guide to single-molecule FRET
Roy, R., Hohng, S., & Ha, T. (2008) · Nature Methods · doi:10.1038/nmeth.1208 · Cited by 2,157 · see citing works
Self-citationHuman Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
Meister, G., Landthaler, M., Patkaniowska, A., Dorsett, Y., Teng, G., & Tuschl, T. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.07.007 · Cited by 1,718 · see citing works
MicroRNA-Directed Cleavage of <i>HOXB8</i> mRNA
Yekta, S., Shih, I.-H., & Bartel, D. P. (2004) · Science · doi:10.1126/science.1097434 · Cited by 1,702 · see citing works
Ventura, A., Young, A. G., Winslow, M. M., Lintault, L., Meissner, A., Erkeland, S. J., Newman, J. J., Bronson, R. T., Crowley, D. G., Stone, J. R., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.019 · Cited by 1,592 · see citing works
A Distinct Small RNA Pathway Silences Selfish Genetic Elements in the Germline
Vagin, V. V., Sigova, A. A., Li, C., Seitz, H., Gvozdev, V. A., & Zamore, P. D. (2006) · Science · doi:10.1126/science.1129333 · Cited by 1,342 · see citing works
RNA Interference: Biology, Mechanism, and Applications
Agrawal, N., Dasaradhi, P. V. N., Mohmmed, A., Malhotra, P., Bhatnagar, R. K., & Mukherjee, S. K. (2003) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.67.4.657-685.2003 · Cited by 1,312 · see citing works
Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes
Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi‐Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., et al. (2008) · Nature · doi:10.1038/nature06908 · Cited by 1,115 · see citing works
Physical chemistry: a molecular approach
(1998) · Choice Reviews Online · doi:10.5860/choice.35-2708 · Cited by 1,081 · see citing works
Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
Tam, O. H., Aravin, A. A., Stein, P., Girard, A., Murchison, E. P., Cheloufi, S., Hodges, E. C., Anger, M., Sachidanandam, R., Schultz, R. M., et al. (2008) · Nature · doi:10.1038/nature06904 · Cited by 1,042 · see citing works
Argonaute2 Cleaves the Anti-Guide Strand of siRNA during RISC Activation
Rand, T., Petersen, S., Du, F., & Wang, X. (2005) · Cell · doi:10.1016/j.cell.2005.10.020 · Cited by 784 · see citing works
Purified Argonaute2 and an siRNA form recombinant human RISC
Rivas, F. V., Tolia, N. H., Song, J., Aragon, J. P., Liu, J., Hannon, G. J., & Joshua‐Tor, L. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb918 · Cited by 760 · see citing works
Self-citationThe Crystal Structure of Human Argonaute2
Schirle, N. T., & MacRae, I. J. (2012) · Science · doi:10.1126/science.1221551 · Cited by 697 · see citing works
Revisiting the principles of microRNA target recognition and mode of action
Brodersen, P., & Voinnet, O. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2619 · Cited by 657 · see citing works
The Structure of Human Argonaute-2 in Complex with miR-20a
Elkayam, E., Kuhn, C., Tocilj, A., Haase, A. D. D., Greene, E. M., Hannon, G. J., & Joshua‐Tor, L. (2012) · Cell · doi:10.1016/j.cell.2012.05.017 · Cited by 615 · see citing works
Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex
Wang, Y., Juranek, S., Li, H., Sheng, G., Tuschl, T., & Patel, D. J. (2008) · Nature · doi:10.1038/nature07666 · Cited by 577 · see citing works
Structural basis for microRNA targeting
Schirle, N. T., Sheu‐Gruttadauria, J., & MacRae, I. J. (2014) · Science · doi:10.1126/science.1258040 · Cited by 563 · see citing works
Desperately seeking microRNA targets
Thomas, M., Lieberman, J., & Lal, A. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1921 · Cited by 476 · see citing works
RNAi-Mediated Allelic trans-Interaction at the Imprinted Rtl1/Peg11 Locus
Davis, E. E., Caiment, F., Tordoir, X., Cavaillé, J., Ferguson‐Smith, A. C., Cockett, N., Georges, M., & Charlier, C. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.060 · Cited by 331 · see citing works
An alternative mode of microRNA target recognition
Chi, S. W., Hannon, G. J., & Darnell, R. B. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2230 · Cited by 328 · see citing works
The role of small RNAs in abiotic stress
Phillips, J., Dalmay, T., & Bartels, D. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.04.007 · Cited by 265 · see citing works
Molecular Insights into microRNA-Mediated Translational Repression in Plants
Iwakawa, H., & Tomari, Y. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.10.033 · Cited by 263 · see citing works
Gene regulation. Structural basis for microRNA targeting.
Schirle, N. T., Sheu‐Gruttadauria, J., & MacRae, I. J. (2014) · Science · doi:10.2210/pdb4w5n/pdb · Cited by 227 · see citing works
Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2
De, N., Young, L. E., Lau, P., Meisner-Kober, N. C., Morrissey, D. V., & MacRae, I. J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.001 · Cited by 131 · see citing works
Single-Molecule Three-Color FRET with Both Negligible Spectral Overlap and Long Observation Time
Lee, S.-H., Lee, J., & Hohng, S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012270 · Cited by 103 · see citing works
Self-citationPlanting the seed: target recognition of short guide RNAs
Künne, T., Swarts, D. C., & Brouns, S. J. J. (2014) · Trends in Microbiology · doi:10.1016/j.tim.2013.12.003 · Cited by 86 · see citing works
Jung, S., Kim, E., Hwang, W., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja403138d · Cited by 43 · see citing works
Self-citationA novel approach for evaluating the efficiency of siRNAs on protein levels in cultured cells
Wu, W. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh010 · Cited by 43 · see citing works
Comparison of Femtosecond Laser and Continuous Wave UV Sources for Protein–Nucleic Acid Crosslinking
Fecko, C. J., Munson, K. M., Saunders, A., Sun, G., Begley, T. P., Lis, J. T., & Webb, W. W. (2007) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2007.00179.x · Cited by 31 · see citing works
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Broughton, J. P., Lovci, M. T., Huang, J. L., Yeo, G. W., & Pasquinelli, A. E. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.09.004 · Cited by 487 · see citing works
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Rani, V., & Sengar, R. S. (2022) · Biotechnology and Bioengineering · doi:10.1002/bit.28029 · Cited by 172 · see citing works
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Becker, W. R., Ober-Reynolds, B., Jouravleva, K., Jolly, S. M., Zamore, P. D., & Greenleaf, W. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.06.012 · Cited by 161 · see citing works
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- Authors
- Jo, M. H., Shin, S., Jung, S.-R., Kim, E., Song, J.-J., & Hohng, S.
- Affiliations
- Seoul National University (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Corresponding author
- Song, Ji-Joon
- Hohng, Sungchul
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 59
- Issue
- 1
- Pages
- 117-124
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1480846517
- Cited by
- 207
- References
- 37
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 16 · 2023: 23 · 2022: 31 · 2021: 30 · 2020: 19 · 2019: 22 · 2018: 9 · 2017: 16 · 2016: 11 · 2015: 4
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- Argonaute 2, RNA-induced silencing complex, RNA silencing, seed region, siRNA design, sequence complementarity, single-molecule fluorescence
- MeSH terms
- Base Sequence, Fluorescence, Humans, RNA, Small Interfering, RNA-Induced Silencing Complex, MicroRNAs, Argonaute Proteins
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