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==Structural Basis of MicroRNA Biogenesis by Dicer-1 and Its Partner Protein Loqs-PB - complex IV==
<StructureSection load='8dga' size='340' side='right'caption='[[8dga]], [[Resolution|resolution]] 3.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dga]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DGA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dga OCA], [https://pdbe.org/8dga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dga RCSB], [https://www.ebi.ac.uk/pdbsum/8dga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dga ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DCR1_DROME 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).<ref>PMID:11201747</ref> <ref>PMID:11498593</ref> <ref>PMID:15066283</ref> <ref>PMID:15918769</ref> <ref>PMID:15985611</ref> <ref>PMID:16949822</ref> <ref>PMID:17666393</ref> <ref>PMID:17928574</ref> <ref>PMID:19451544</ref> <ref>PMID:19635780</ref> <ref>PMID:21419681</ref> <ref>PMID:21926993</ref> <ref>PMID:23063653</ref> <ref>PMID:24488111</ref> <ref>PMID:36182693</ref> 
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== 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 LoqsâPB 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 Dicerâ1âLoqsâPB heterodimer. The Dicer-1 dsRBD and three LoqsâPB 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 Dicerâ1âLoqsâPB 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<ref>PMID:36182693</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8dga" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Demo G]]
[[Category: Dutcher RC]]
[[Category: Golovenko D]]
[[Category: Jouravleva K]]
[[Category: Korostelev AA]]
[[Category: Tanaka Hall TM]]
[[Category: Zamore PD]]