8dgj

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

Structural highlights

8dgj is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.02Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DCR1_DROME Endoribonuclease which functions in microRNA- (miRNA) gene silencing and, independently of its ribonuclease III activity, also acts in the short interfering RNA- (siRNA) gene silencing pathway (PubMed:11201747, PubMed:11498593, PubMed:15066283, PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19451544, PubMed:19635780, PubMed:21419681, PubMed:21926993, PubMed:24488111, PubMed:36182693). Cleaves hairpin precursor miRNAs (pre-miRNA) to generate mature miRNAs (miRNAs) that are between twenty-one to twenty-four nucleotides in length and function in RNA silencing and post-transcriptional regulation of gene expression (PubMed:15066283, PubMed:15918769, PubMed:15985611, PubMed:17666393, PubMed:17928574, PubMed:19451544, PubMed:19635780, PubMed:21419681, PubMed:21926993, PubMed:23063653, PubMed:24488111, PubMed:36182693). Also functions in miRNA loading and assembly of the Argonaute 1 (AGO1)-containing RNA-induced silencing complex (miRISC), with the miRNAs serving as a guide to direct the miRISC to complementary RNAs to degrade them or prevent their translation (PubMed:15066283, PubMed:17928574, PubMed:19451544). Independently of its catalytic activity, functions in the siRNA silencing pathway by promoting assembly of the siRNA-directed Argonaute 2 (AGO2)-containing RISC (siRISC) (PubMed:15066283). Required for the proper formation of a stable intermediate (R2) in siRISC assembly, which is formed from the R1 precursor complex (containing Dcr-2, R2D2 and the siRNA) and is used for assembly of the mature (R3) siRISC complex (PubMed:15066283). It is not required for siRNA biogenesis (PubMed:15066283, PubMed:21419681). During embryogenesis, involved in germline fate determination (PubMed:16949822).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]

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 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.

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[16]

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

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Citations
6 reviews cite this structure
microRNAs in action: biogenesis, function and regulation.
Shang et al. (2023)
5 more
8 other articles
No citations found

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. ↑ Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell. 2004 Apr 2;117(1):69-81. PMID:15066283 doi:10.1016/s0092-8674(04)00261-2
  4. ↑ Saito K, Ishizuka A, Siomi H, Siomi MC. Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol. 2005 Jul;3(7):e235. PMID:15918769 doi:10.1371/journal.pbio.0030235
  5. ↑ Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev. 2005 Jul 15;19(14):1674-9. PMID:15985611 doi:10.1101/gad.1334005
  6. ↑ 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
  7. ↑ Ye X, Paroo Z, Liu Q. Functional anatomy of the Drosophila microRNA-generating enzyme. J Biol Chem. 2007 Sep 28;282(39):28373-28378. PMID:17666393 doi:10.1074/jbc.M705208200
  8. ↑ Liu X, Park JK, Jiang F, Liu Y, McKearin D, Liu Q. Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes. RNA. 2007 Dec;13(12):2324-9. PMID:17928574 doi:10.1261/rna.723707
  9. ↑ Miyoshi K, Okada TN, Siomi H, Siomi MC. Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway. RNA. 2009 Jul;15(7):1282-91. PMID:19451544 doi:10.1261/rna.1541209
  10. ↑ Zhou R, Czech B, Brennecke J, Sachidanandam R, Wohlschlegel JA, Perrimon N, Hannon GJ. Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform. RNA. 2009 Oct;15(10):1886-95. PMID:19635780 doi:10.1261/rna.1611309
  11. ↑ Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD. Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease. Mol Cell. 2011 Apr 22;42(2):172-84. PMID:21419681 doi:10.1016/j.molcel.2011.03.002
  12. ↑ Tsutsumi A, Kawamata T, Izumi N, Seitz H, Tomari Y. Recognition of the pre-miRNA structure by Drosophila Dicer-1. Nat Struct Mol Biol. 2011 Sep 18;18(10):1153-8. PMID:21926993 doi:10.1038/nsmb.2125
  13. ↑ Fukunaga R, Han BW, Hung JH, Xu J, Weng Z, Zamore PD. Dicer partner proteins tune the length of mature miRNAs in flies and mammals. Cell. 2012 Oct 26;151(3):533-46. PMID:23063653 doi:10.1016/j.cell.2012.09.027
  14. ↑ Fukunaga R, Colpan C, Han BW, Zamore PD. Inorganic phosphate blocks binding of pre-miRNA to Dicer-2 via its PAZ domain. EMBO J. 2014 Feb 18;33(4):371-84. PMID:24488111 doi:10.1002/embj.201387176
  15. ↑ 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
  16. ↑ 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

Contents


PDB ID 8dgj

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