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| | <StructureSection load='6lxe' size='340' side='right'caption='[[6lxe]], [[Resolution|resolution]] 4.20Å' scene=''> | | <StructureSection load='6lxe' size='340' side='right'caption='[[6lxe]], [[Resolution|resolution]] 4.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lxe]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LXE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LXE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lxe]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LXE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DROSHA, RN3, RNASE3L, RNASEN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DGCR8, C22orf12, DGCRK6, LP4941 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonuclease_III Ribonuclease III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.3 3.1.26.3] </span></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=6lxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lxe OCA], [https://pdbe.org/6lxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lxe RCSB], [https://www.ebi.ac.uk/pdbsum/6lxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lxe ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lxe OCA], [http://pdbe.org/6lxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lxe RCSB], [http://www.ebi.ac.uk/pdbsum/6lxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lxe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RNC_HUMAN RNC_HUMAN]] Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.<ref>PMID:10948199</ref> <ref>PMID:14508493</ref> <ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:15565168</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:17159994</ref> [[http://www.uniprot.org/uniprot/DGCR8_HUMAN DGCR8_HUMAN]] Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Involved in the silencing of embryonic stem cells self-renewal.<ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:16963499</ref> <ref>PMID:17159994</ref> | + | [https://www.uniprot.org/uniprot/RNC_HUMAN RNC_HUMAN] Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.<ref>PMID:10948199</ref> <ref>PMID:14508493</ref> <ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:15565168</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:17159994</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | A commencing and critical step in miRNA biogenesis involves processing of pri-miRNAs in the nucleus by Microprocessor. An important, but not completely understood, question is how Drosha, the catalytic subunit of Microprocessor, binds pri-miRNAs and correctly specifies cleavage sites. Here we report the cryoelectron microscopy structures of the Drosha-DGCR8 complex with and without a pri-miRNA. The RNA-bound structure provides direct visualization of the tertiary structure of pri-miRNA and shows that a helix hairpin in the extended PAZ domain and the mobile basic (MB) helix in the RNase IIIa domain of Drosha coordinate to recognize the single-stranded to double-stranded junction of RNA, whereas the dsRNA binding domain makes extensive contacts with the RNA stem. Furthermore, the RNA-free structure reveals an autoinhibitory conformation of the PAZ helix hairpin. These findings provide mechanistic insights into pri-miRNA cleavage site selection and conformational dynamics governing pri-miRNA recognition by the catalytic component of Microprocessor.
| + | |
| - | | + | |
| - | Structural Basis for pri-miRNA Recognition by Drosha.,Jin W, Wang J, Liu CP, Wang HW, Xu RM Mol Cell. 2020 Mar 25. pii: S1097-2765(20)30144-1. doi:, 10.1016/j.molcel.2020.02.024. PMID:32220645<ref>PMID:32220645</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6lxe" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ribonuclease III]]
| + | [[Category: Jin W]] |
| - | [[Category: Jin, W]] | + | [[Category: Liu CP]] |
| - | [[Category: Liu, C P]] | + | [[Category: Wang HW]] |
| - | [[Category: Wang, H W]] | + | [[Category: Wang J]] |
| - | [[Category: Wang, J]] | + | [[Category: Xu RM]] |
| - | [[Category: Xu, R M]] | + | |
| - | [[Category: Hydrolase-rna binding protein complex]]
| + | |
| - | [[Category: Ribonuclease]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
RNC_HUMAN Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.[1] [2] [3] [4] [5] [6] [7] [8] [9]
References
- ↑ Wu H, Xu H, Miraglia LJ, Crooke ST. Human RNase III is a 160-kDa protein involved in preribosomal RNA processing. J Biol Chem. 2000 Nov 24;275(47):36957-65. PMID:10948199 doi:http://dx.doi.org/10.1074/jbc.M005494200
- ↑ Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003 Sep 25;425(6956):415-9. PMID:14508493 doi:http://dx.doi.org/10.1038/nature01957
- ↑ Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004 Dec 14;14(23):2162-7. PMID:15589161 doi:10.1016/j.cub.2004.11.001
- ↑ Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004 Dec 15;18(24):3016-27. Epub 2004 Dec 1. PMID:15574589 doi:10.1101/gad.1262504
- ↑ Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004 Nov 11;432(7014):235-40. Epub 2004 Nov 7. PMID:15531877 doi:10.1038/nature03120
- ↑ Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005 Jan 12;24(1):138-48. Epub 2004 Nov 25. PMID:15565168 doi:http://dx.doi.org/10.1038/sj.emboj.7600491
- ↑ Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006 Jun 2;125(5):887-901. PMID:16751099 doi:10.1016/j.cell.2006.03.043
- ↑ Pauley KM, Eystathioy T, Jakymiw A, Hamel JC, Fritzler MJ, Chan EK. Formation of GW bodies is a consequence of microRNA genesis. EMBO Rep. 2006 Sep;7(9):904-10. Epub 2006 Aug 11. PMID:16906129 doi:7400783
- ↑ Faller M, Matsunaga M, Yin S, Loo JA, Guo F. Heme is involved in microRNA processing. Nat Struct Mol Biol. 2007 Jan;14(1):23-9. Epub 2006 Dec 10. PMID:17159994 doi:10.1038/nsmb1182
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