Proteopedia

8dga

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Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IVStructural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IV

Structural highlights

8dga is a 4 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DCR1_DROME Essential for RNA interference (RNAi); double-stranded RNA (dsRNA) induces potent and specific gene silencing. RNAi is mediated by the RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys or silences messenger RNAs homologous to the silencing trigger. May carry out the initiation step of RNAi by cleaving dsRNA to produce 22 bp dsRNAs (siRNAs) which target the selective destruction of homologous RNAs. During embryogenesis, involved in germline fate determination.[1] [2] [3]

Publication Abstract from PubMed

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 LoqsPB 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 Dicer1LoqsPB heterodimer. The Dicer-1 dsRBD and three LoqsPB 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 Dicer1LoqsPB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.

Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.,Jouravleva K, Golovenko D, Demo G, Dutcher RC, Hall TMT, Zamore PD, Korostelev AA Mol Cell. 2022 Nov 3;82(21):4049-4063.e6. doi: 10.1016/j.molcel.2022.09.002. Epub, 2022 Sep 30. PMID:36182693[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001 Jan 18;409(6818):363-6. PMID:11201747 doi:http://dx.doi.org/10.1038/35053110
  2. ↑ Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science. 2001 Aug 10;293(5532):1146-50. PMID:11498593 doi:http://dx.doi.org/10.1126/science.1064023
  3. ↑ Megosh HB, Cox DN, Campbell C, Lin H. The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr Biol. 2006 Oct 10;16(19):1884-94. doi: 10.1016/j.cub.2006.08.051. Epub 2006 , Aug 31. PMID:16949822 doi:http://dx.doi.org/10.1016/j.cub.2006.08.051
  4. ↑ Jouravleva K, Golovenko D, Demo G, Dutcher RC, Hall TMT, Zamore PD, Korostelev AA. Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB. Mol Cell. 2022 Nov 3;82(21):4049-4063.e6. doi: 10.1016/j.molcel.2022.09.002. Epub, 2022 Sep 30. PMID:36182693 doi:http://dx.doi.org/10.1016/j.molcel.2022.09.002

8dga, resolution 3.73Å

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