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| | <StructureSection load='5w0o' size='340' side='right'caption='[[5w0o]], [[Resolution|resolution]] 2.49Å' scene=''> | | <StructureSection load='5w0o' size='340' side='right'caption='[[5w0o]], [[Resolution|resolution]] 2.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w0o]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W0O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w0o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W0O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.488Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_uridylyltransferase RNA uridylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.52 2.7.7.52] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></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=5w0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0o OCA], [http://pdbe.org/5w0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0o RCSB], [http://www.ebi.ac.uk/pdbsum/5w0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0o 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=5w0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0o OCA], [https://pdbe.org/5w0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w0o RCSB], [https://www.ebi.ac.uk/pdbsum/5w0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TUT7_HUMAN TUT7_HUMAN]] Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult.<ref>PMID:19703396</ref> <ref>PMID:22898984</ref> <ref>PMID:25480299</ref> | + | [https://www.uniprot.org/uniprot/TUT7_HUMAN TUT7_HUMAN] Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult.<ref>PMID:19703396</ref> <ref>PMID:22898984</ref> <ref>PMID:25480299</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5w0o" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5w0o" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[RNA uridylyltransferase|RNA uridylyltransferase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA uridylyltransferase]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Faehnle, C R]] | + | [[Category: Faehnle CR]] |
| - | [[Category: Joshua-Tor, L]] | + | [[Category: Joshua-Tor L]] |
| - | [[Category: Walleshauser, J]] | + | [[Category: Walleshauser J]] |
| - | [[Category: Terminal uridyltransferase]]
| + | |
| - | [[Category: Transferase-rna complex]]
| + | |
| - | [[Category: Tutase]]
| + | |
| Structural highlights
Function
TUT7_HUMAN Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult.[1] [2] [3]
Publication Abstract from PubMed
The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins to favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.
Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.,Faehnle CR, Walleshauser J, Joshua-Tor L Nat Struct Mol Biol. 2017 Aug;24(8):658-665. doi: 10.1038/nsmb.3428. Epub 2017, Jul 3. PMID:28671666[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Heo I, Joo C, Kim YK, Ha M, Yoon MJ, Cho J, Yeom KH, Han J, Kim VN. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009 Aug 21;138(4):696-708. doi: 10.1016/j.cell.2009.08.002. PMID:19703396 doi:http://dx.doi.org/10.1016/j.cell.2009.08.002
- ↑ Thornton JE, Chang HM, Piskounova E, Gregory RI. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA. 2012 Oct;18(10):1875-85. doi: 10.1261/rna.034538.112. Epub 2012 Aug 16. PMID:22898984 doi:http://dx.doi.org/10.1261/rna.034538.112
- ↑ Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, Kim VN. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell. 2014 Dec 4;159(6):1365-76. doi: 10.1016/j.cell.2014.10.055. PMID:25480299 doi:http://dx.doi.org/10.1016/j.cell.2014.10.055
- ↑ Faehnle CR, Walleshauser J, Joshua-Tor L. Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis. Nat Struct Mol Biol. 2017 Aug;24(8):658-665. doi: 10.1038/nsmb.3428. Epub 2017, Jul 3. PMID:28671666 doi:http://dx.doi.org/10.1038/nsmb.3428
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