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Conserved asymmetry underpins homodimerization of Dicer-associated double-stranded RNA-binding proteins

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JournalNucleic Acids Research
DateAccepted/In press - 9 Oct 2017
DatePublished (current) - 1 Dec 2017
Issue number21
Volume45
Number of pages8
Pages (from-to)12577-12584
Original languageEnglish

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.

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    Research areas

  • Humans, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Protein Domains, Protein Multimerization, RNA, Double-Stranded, RNA-Binding Proteins, Journal Article

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