Data availability
The cryo-EM structure of AMC–let-7a-1 has been deposited in the PDB under accession code 9W5I . The composite map and consensus map of AMC–let-7a-1 have been deposited in the EMDB under accession codes EMD-65663 and EMD-65662 , respectively. The partial maps of local refinement focused on MID/PIWI, N-domain and HSP90–p23 have been deposited in the EMDB under accession codes EMD-65661 , EMD-65660 and EMD-65659 , respectively. The consensus map and AGO2-focused map of AMC have been deposited in the EMDB under accession codes EMD-69544 and EMD-65658 , respectively. There are no restrictions on data availability. For material requests, please contact the corresponding authors. Other structural models cited in this study for analysis ( 4W5N , 4W5O , 7KRJ , 7XW2 , 8EOB , 9CMP , 7V6C , 7ZUB , 8FFW , 5FWK , 5FWL , 7Z37 and 8GFT ) are also available at the PDB.
References
Iwasaki, S. et al. Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Mol. Cell 39 , 292–299 (2010).
Article
CAS
PubMed
Google Scholar
Miyoshi, T., Takeuchi, A., Siomi, H. & Siomi, M. C. A direct role for Hsp90 in pre-RISC formation in Drosophila . Nat. Struct. Mol. Biol. 17 , 1024–1026 (2010).
Article
CAS
PubMed
Google Scholar
Iki, T. et al. In vitro assembly of plant RNA-induced silencing complexes facilitated by molecular chaperone HSP90. Mol. Cell 39 , 282–291 (2010).
Article
CAS
PubMed
Google Scholar
Kim, H., Lee, Y.-Y. & Kim, V. N. The biogenesis and regulation of animal microRNAs. Nat. Rev. Mol. Cell Biol. 26 , 276–296 (2025).
Article
CAS
PubMed
Google Scholar
Matranga, C., Tomari, Y., Shin, C., Bartel, D. P. & Zamore, P. D. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123 , 607–620 (2005).
Article
ADS
CAS
PubMed
Google Scholar
Schirle, N. T. & MacRae, I. J. The crystal structure of human Argonaute2. Science 336 , 1037–1040 (2012).
Article
ADS
CAS
PubMed
PubMed Central
Google Scholar
Elkayam, E. et al. The structure of human argonaute-2 in complex with miR-20a. Cell 150 , 233 (2012).
Article
CAS
Google Scholar
Song, J.-J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305 , 1434–1437 (2004).
Article
ADS
CAS
PubMed
Google Scholar
Iwakawa, H.-O. & Tomari, Y. Life of RISC: formation, action, and degradation of RNA-induced silencing complex. Mol. Cell 82 , 30–43 (2022).
Article
CAS
PubMed
Google Scholar
Kirschke, E., Goswami, D., Southworth, D., Griffin, P. R. & Agard, D. A. Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell 157 , 1685–1697 (2014).
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang, R. Y.-R. et al. Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism. Nature 601 , 460–464 (2022).
Article
ADS
CAS
PubMed
Google Scholar
Noddings, C. M., Wang, R. Y.-R., Johnson, J. L. & Agard, D. A. Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism. Nature 601 , 465–469 (2022).
Article
ADS
CAS
PubMed
Google Scholar
Iwasaki, S. et al. Defining fundamental steps in the assembly of the Drosophila RNAi enzyme complex. Nature 521 , 533–536 (2015).
Article
ADS
CAS
PubMed
Google Scholar
Naruse, K., Matsuura-Suzuki, E., Watanabe, M., Iwasaki, S. & Tomari, Y. In vitro reconstitution of chaperone-mediated human RISC assembly. RNA 24 , 6–11 (2018).
Article
CAS
PubMed
Google Scholar
Tsuboyama, K., Tadakuma, H. & Tomari, Y. Conformational activation of Argonaute by distinct yet coordinated actions of the Hsp70 and Hsp90 chaperone systems. Mol. Cell 70 , 722–729 (2018).
Article
CAS
PubMed
Google Scholar
Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305 , 1437–1441 (2004).
Article
ADS
CAS
PubMed
Google Scholar
Landthaler, M. et al. Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA 14 , 2580–2596 (2008).
Article
CAS
PubMed
PubMed Central
Google Scholar
Verba, K. A. et al. Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase. Science 352 , 1542–1547 (2016).
Article
ADS
CAS
PubMed
PubMed Central
Google Scholar
Suzuki, H. I. et al. Small-RNA asymmetry is directly driven by mammalian Argonautes. Nat. Struct. Mol. Biol. 22 , 512–521 (2015).
Article
ADS
CAS
PubMed
Google Scholar
Winter, J. & Diederichs, S. Argonaute-3 activates the let-7a passenger strand microRNA. RNA Biol. 10 , 1631–1643 (2013).
Article
PubMed
PubMed Central
Google Scholar
Kobayashi, H., Shoji, K., Kiyokawa, K., Negishi, L. & Tomari, Y. Iruka eliminates dysfunctional Argonaute by selective ubiquitination of its empty state. Mol. Cell 73…
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