5f5f: Difference between revisions
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The | ==X-ray structure of Roquin ROQ domain in complex with a Selex-derived hexa-loop RNA motif== | ||
<StructureSection load='5f5f' size='340' side='right'caption='[[5f5f]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5f5f]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F5F FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</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=5f5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5f OCA], [https://pdbe.org/5f5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f5f RCSB], [https://www.ebi.ac.uk/pdbsum/5f5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RC3H1_MOUSE RC3H1_MOUSE] Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs (PubMed:23663784). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation.<ref>PMID:15917799</ref> <ref>PMID:18172933</ref> <ref>PMID:20412057</ref> <ref>PMID:20639877</ref> <ref>PMID:23663784</ref> <ref>PMID:23583643</ref> <ref>PMID:23583642</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 3'-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin. | |||
Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40.,Janowski R, Heinz GA, Schlundt A, Wommelsdorf N, Brenner S, Gruber AR, Blank M, Buch T, Buhmann R, Zavolan M, Niessing D, Heissmeyer V, Sattler M Nat Commun. 2016 Mar 24;7:11032. doi: 10.1038/ncomms11032. PMID:27010430<ref>PMID:27010430</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5f5f" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Sattler | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Janowski R]] | |||
[[Category: Niessing D]] | |||
[[Category: Sattler M]] | |||
[[Category: Schlundt A]] | |||
Latest revision as of 11:47, 12 July 2023
X-ray structure of Roquin ROQ domain in complex with a Selex-derived hexa-loop RNA motifX-ray structure of Roquin ROQ domain in complex with a Selex-derived hexa-loop RNA motif
Structural highlights
FunctionRC3H1_MOUSE Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs (PubMed:23663784). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 3'-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin. Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40.,Janowski R, Heinz GA, Schlundt A, Wommelsdorf N, Brenner S, Gruber AR, Blank M, Buch T, Buhmann R, Zavolan M, Niessing D, Heissmeyer V, Sattler M Nat Commun. 2016 Mar 24;7:11032. doi: 10.1038/ncomms11032. PMID:27010430[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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