Structural determinants of miRNAs for RISC loading and slicer-independent unwinding
Abstract
MicroRNAs (miRNAs) regulate expression of their target mRNAs through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) family protein as a core component. In Drosophila melanogaster, miRNAs are generally sorted into Ago1-containing RISC (Ago1-RISC). We established a native gel system that can biochemically dissect the Ago1-RISC assembly pathway. We found that miRNA-miRNA* duplexes are loaded into Ago1 as double-stranded RNAs in an ATP-dependent fashion. In contrast, unexpectedly, unwinding of miRNA-miRNA* duplexes is a passive process that does not require ATP or slicer activity of Ago1. Central mismatches direct miRNA-miRNA* duplexes into pre-Ago1-RISC, whereas mismatches in the seed or guide strand positions 12-15 promote conversion of pre-Ago1-RISC into mature Ago1-RISC. Our findings show that unwinding of miRNAs is a precise mirror-image process of target recognition, and both processes reflect the unique geometry of RNAs in Ago proteins.
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Fly Dcr-1 is not required for incorporation of miRNA::miRNA* duplexes into Ago1/miRISC.
“and fly Dcr‐1 is not required for incorporation of miRNA::miRNA* duplexes into Ago1/miRISC (Kawamata, Seitz, & Tomari, 2009; Yoda et al., 2009).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Kawamata, Seitz, & Tomari, 2009
Cites
The impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592 · see citing works
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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 · see citing works
Kawamata, T., & Tomari, Y. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.03.009 · Cited by 481 · see citing works
Self-citationLife of RISC: Formation, action, and degradation of RNA-induced silencing complex
Iwakawa, H.-O., & Tomari, Y. (2022) · Molecular Cell · doi:10.1016/j.molcel.2021.11.026 · Cited by 488 · see citing works
Self-citationATP-dependent human RISC assembly pathways
Yoda, M., Kawamata, T., Paroo, Z., Ye, X., Iwasaki, S., Liu, Q., & Tomari, Y. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1733 · Cited by 380 · see citing works
Self-citationmicroRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225 · see citing works
- Authors
- Kawamata, T., Seitz, H., & Tomari, Y.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2009-08-16
- Volume
- 16
- Issue
- 9
- Pages
- 953-960
- ISSN
- 1545-9993
- 1545-9985
- Cited by
- 269
- References
- 1
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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