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| | <StructureSection load='4pmw' size='340' side='right'caption='[[4pmw]], [[Resolution|resolution]] 2.95Å' scene=''> | | <StructureSection load='4pmw' size='340' side='right'caption='[[4pmw]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pmw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PMW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PMW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pmw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PMW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PMW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dis3l2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4pmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pmw OCA], [https://pdbe.org/4pmw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pmw RCSB], [https://www.ebi.ac.uk/pdbsum/4pmw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pmw ProSAT]</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=4pmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pmw OCA], [http://pdbe.org/4pmw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pmw RCSB], [http://www.ebi.ac.uk/pdbsum/4pmw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pmw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DI3L2_MOUSE DI3L2_MOUSE]] 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation.<ref>PMID:23594738</ref> | + | [https://www.uniprot.org/uniprot/DI3L2_MOUSE DI3L2_MOUSE] 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation.<ref>PMID:23594738</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Faehnle, C R]] | + | [[Category: Unidentified]] |
| - | [[Category: Joshua-Tor, L]] | + | [[Category: Faehnle CR]] |
| - | [[Category: Walleshauser, J]] | + | [[Category: Joshua-Tor L]] |
| - | [[Category: Exonuclease]]
| + | [[Category: Walleshauser J]] |
| - | [[Category: Hydrolase-rna complex]]
| + | |
| - | [[Category: Mirna regulation]] | + | |
| - | [[Category: Rna complex]]
| + | |
| - | [[Category: Rna interference]]
| + | |
| Structural highlights
Function
DI3L2_MOUSE 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation.[1]
Publication Abstract from PubMed
The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development, glucose metabolism and tissue regeneration. Overexpression of Lin28 is correlated with the onset of numerous cancers, whereas let-7, a tumour suppressor, silences several human oncogenes. Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo-uridylation activity of TUT4 and TUT7 (refs 10, 11, 12). The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.
Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway.,Faehnle CR, Walleshauser J, Joshua-Tor L Nature. 2014 Aug 3. doi: 10.1038/nature13553. PMID:25119025[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chang HM, Triboulet R, Thornton JE, Gregory RI. A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature. 2013 May 9;497(7448):244-8. doi: 10.1038/nature12119. Epub 2013 Apr 17. PMID:23594738 doi:http://dx.doi.org/10.1038/nature12119
- ↑ Faehnle CR, Walleshauser J, Joshua-Tor L. Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway. Nature. 2014 Aug 3. doi: 10.1038/nature13553. PMID:25119025 doi:http://dx.doi.org/10.1038/nature13553
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