Heyam, Alex, Coupland, Claire E, Dégut, Clément et al. (8 more authors) (2017) Conserved asymmetry underpins homodimerization of Dicer-associated double-stranded RNA-binding proteins. Nucleic Acids Research. pp. 12577-12584. ISSN 0305-1048
Abstract
Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs). In each case, the interaction involves a region of the protein that contains a Type B dsRBD. All three dsRBPs are reported to homodimerize, with the Dicer-binding region implicated in self-association. We report that these dsRBD homodimers display structural asymmetry and that this unusual self-association mechanism is conserved from flies to humans. We show that the core dsRBD is sufficient for homodimerization and that mutation of a conserved leucine residue abolishes self-association. We attribute differences in the self-association properties of Loqs, TRBP and PACT to divergence of the composition of the homodimerization interface. Modifications that make TRBP more like PACT enhance self-association. These data are examined in the context of miRNA biogenesis and the protein/protein interaction properties of Type B dsRBDs.
Metadata
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Copyright, Publisher and Additional Information: | © 2017 Oxford University Press. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. | ||||||||
Keywords: | Humans, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Protein Domains, Protein Multimerization, RNA, Double-Stranded, RNA-Binding Proteins, Journal Article | ||||||||
Dates: |
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Institution: | The University of York | ||||||||
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
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Funding Information: |
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Depositing User: | Pure (York) | ||||||||
Date Deposited: | 24 Oct 2017 08:30 | ||||||||
Last Modified: | 06 Dec 2023 12:07 | ||||||||
Published Version: | https://doi.org/10.1093/nar/gkx928 | ||||||||
Status: | Published | ||||||||
Refereed: | Yes | ||||||||
Identification Number: | https://doi.org/10.1093/nar/gkx928 |