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| | ==Structural insights into RISC assembly facilitated by dsRNA binding domains of human RNA helicase (DHX9)== | | ==Structural insights into RISC assembly facilitated by dsRNA binding domains of human RNA helicase (DHX9)== |
| - | <StructureSection load='3vyx' size='340' side='right' caption='[[3vyx]], [[Resolution|resolution]] 2.29Å' scene=''> | + | <StructureSection load='3vyx' size='340' side='right'caption='[[3vyx]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vyx]] 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=3VYX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VYX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vyx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VYX FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vyy|3vyy]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vyy|3vyy]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHX9, DDX9, LKP, NDH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHX9, DDX9, LKP, NDH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vyx OCA], [http://pdbe.org/3vyx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vyx RCSB], [http://www.ebi.ac.uk/pdbsum/3vyx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vyx ProSAT]</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=3vyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vyx OCA], [https://pdbe.org/3vyx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vyx RCSB], [https://www.ebi.ac.uk/pdbsum/3vyx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vyx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DHX9_HUMAN DHX9_HUMAN]] Unwinds double-stranded DNA and RNA in a 3' to 5' direction. Alteration of secondary structure may subsequently influence interactions with proteins or other nucleic acids. Functions as a transcriptional activator. Component of the CRD-mediated complex that promotes MYC mRNA stability. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. Positively regulates HIV-1 LTR-directed gene expression.<ref>PMID:19029303</ref> <ref>PMID:19229320</ref> <ref>PMID:22190748</ref> | + | [[https://www.uniprot.org/uniprot/DHX9_HUMAN DHX9_HUMAN]] Unwinds double-stranded DNA and RNA in a 3' to 5' direction. Alteration of secondary structure may subsequently influence interactions with proteins or other nucleic acids. Functions as a transcriptional activator. Component of the CRD-mediated complex that promotes MYC mRNA stability. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. Positively regulates HIV-1 LTR-directed gene expression.<ref>PMID:19029303</ref> <ref>PMID:19229320</ref> <ref>PMID:22190748</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Helicase|Helicase]] | + | *[[Helicase 3D structures|Helicase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: RNA helicase]] | | [[Category: RNA helicase]] |
| | [[Category: Fu, Q]] | | [[Category: Fu, Q]] |
| Structural highlights
Function
[DHX9_HUMAN] Unwinds double-stranded DNA and RNA in a 3' to 5' direction. Alteration of secondary structure may subsequently influence interactions with proteins or other nucleic acids. Functions as a transcriptional activator. Component of the CRD-mediated complex that promotes MYC mRNA stability. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms. Positively regulates HIV-1 LTR-directed gene expression.[1] [2] [3]
Publication Abstract from PubMed
Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.
Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).,Fu Q, Yuan YA Nucleic Acids Res. 2013 Jan 29. PMID:23361462[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
- ↑ Sadler AJ, Latchoumanin O, Hawkes D, Mak J, Williams BR. An antiviral response directed by PKR phosphorylation of the RNA helicase A. PLoS Pathog. 2009 Feb;5(2):e1000311. doi: 10.1371/journal.ppat.1000311. Epub 2009, Feb 20. PMID:19229320 doi:http://dx.doi.org/10.1371/journal.ppat.1000311
- ↑ Manojlovic Z, Stefanovic B. A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs. RNA. 2012 Feb;18(2):321-34. doi: 10.1261/rna.030288.111. Epub 2011 Dec 21. PMID:22190748 doi:http://dx.doi.org/10.1261/rna.030288.111
- ↑ Fu Q, Yuan YA. Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9). Nucleic Acids Res. 2013 Jan 29. PMID:23361462 doi:http://dx.doi.org/10.1093/nar/gkt042
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