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TitleStructural mechanism of R2D2 and Loqs-PD synergistic modulation on DmDcr-2 oligomers.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 5228, Year 2023
Publish dateAug 26, 2023
AuthorsTing Deng / Shichen Su / Xun Yuan / Jinqiu He / Ying Huang / Jinbiao Ma / Jia Wang /
PubMed AbstractSmall interference RNAs are the key components of RNA interference, a conserved RNA silencing or viral defense mechanism in many eukaryotes. In Drosophila melanogaster, Dicer-2 (DmDcr-2)-mediated ...Small interference RNAs are the key components of RNA interference, a conserved RNA silencing or viral defense mechanism in many eukaryotes. In Drosophila melanogaster, Dicer-2 (DmDcr-2)-mediated RNAi pathway plays important roles in defending against viral infections and protecting genome integrity. During the maturation of siRNAs, two cofactors can regulate DmDcr-2's functions: Loqs-PD that is required for dsRNA processing, and R2D2 that is essential for the subsequent loading of siRNAs into effector Ago2 to form RISC complexes. However, due to the lack of structural information, it is still unclear whether R2D2 and Loqs-PD affect the functions of DmDcr-2 simultaneously. Here we present several cryo-EM structures of DmDcr-2/R2D2/Loqs-PD complex bound to dsRNAs with various lengths by the Helicase domain. These structures revealed that R2D2 and Loqs-PD can bind to different regions of DmDcr-2 without interfering with each other. Furthermore, the cryo-EM results demonstrate that these complexes can form large oligomers and assemble into fibers. The formation and depolymerization of these oligomers are associated with ATP hydrolysis. These findings provide insights into the structural mechanism of DmDcr-2 and its cofactors during siRNA processing.
External linksNat Commun / PubMed:37633971 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 3.74 Å
Structure data

34707

8hf0

EMDB-34707, PDB-8hf0:
DmDcr-2/R2D2/LoqsPD with 50bp-dsRNA in Dimer state
Method: EM (single particle) / Resolution: 3.72 Å

34708

8hf1

EMDB-34708, PDB-8hf1:
DmDcr-2/R2D2/LoqsPD with 19bp-dsRNA in Trimer state
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-34709: DmDcr-2/R2D2/LoqsPD with 50bp-dsRNA in Trimer state
Method: EM (single particle) / Resolution: 3.74 Å

Source
  • drosophila melanogaster (fruit fly)
KeywordsRNA BINDING PROTEIN/RNA / Ribonuclease / DOUBLE STRANDED RNA / RNA BINDING PROTEIN-RNA COMPLEX

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