Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB
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Abstract
In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding domain (dsRBD) proteins to convert precursor-microRNAs (pre-miRNAs) into miRNA duplexes. We report six cryo-EM structures of Drosophila Dicer-1 that show how Dicer-1 and its partner Loqs‑PB cooperate (1) before binding pre-miRNA, (2) after binding and in a catalytically competent state, (3) after nicking one arm of the pre-miRNA, and (4) following complete dicing and initial product release. Our reconstructions suggest that pre-miRNA binds a rare, open conformation of the Dicer‑1⋅Loqs‑PB heterodimer. The Dicer-1 dsRBD and three Loqs‑PB dsRBDs form a tight belt around the pre-miRNA, distorting the RNA helix to place the scissile phosphodiester bonds in the RNase III active sites. Pre-miRNA cleavage shifts the dsRBDs and partially closes Dicer-1, which may promote product release. Our data suggest a model for how the Dicer‑1⋅Loqs‑PB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808 · see citing works
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- Authors
- Jouravleva, K., Golovenko, D., Demo, G., Dutcher, R. C., Hall, T. M. T., Zamore, P. D., & Korostelev, A. A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hall, Traci M. Tanaka
- Zamore, Phillip D.
- Korostelev, Andrei A.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 82
- Issue
- 21
- Pages
- 4049-4063.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC9637774
- OpenAlex
- W4298111957
- Cited by
- 57
- References
- 2
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 9 · 2023: 18 · 2022: 3
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Charles A. King Trust
- National Institutes of Health
- University of Massachusetts Medical School
- National Institute of General Medical Sciences (R35GM136275, R35GM127094)
- National Institute of Environmental Health Sciences (ZIAES050165)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- 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
- DICER1, microRNA biogenesis, pre-miRNA processing, double-stranded RNA-binding domain, Drosophila, cryo-EM structure, product launch, endonuclease activity
- MeSH terms
- Animals, Drosophila, RNA-Binding Proteins, Drosophila Proteins, MicroRNAs, Ribonuclease III
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