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2rq4

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Revision as of 08:45, 12 September 2018

Refinement of RNA binding domain 3 in CUG triplet repeat RNA-binding protein 1

Structural highlights

2rq4 is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2cpz
Gene:	CUGBP1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CELF1_HUMAN] RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Activates SM exon 5 inclusion by antagonizing the repressive effect of PTB. Promotes exclusion of exon 11 of the INSR pre-mRNA. Inhibits, together with HNRNPH1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Increases translation and controls the choice of translation initiation codon of CEBPB mRNA. Increases mRNA translation of CEBPB in aging liver (By similarity). Increases translation of CDKN1A mRNA by antagonizing the repressive effect of CALR3. Mediates rapid cytoplasmic mRNA deadenylation. Recruits the deadenylase PARN to the poly(A) tail of EDEN-containing mRNAs to promote their deadenylation. Required for completion of spermatogenesis (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK and to Bruno response elements (BREs). Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. Binds to AU-rich sequences (AREs or EDEN-like) localized in the 3'-UTR of JUN and FOS mRNAs. Binds to the IR RNA. Binds to the 5'-region of CDKN1A and CEBPB mRNAs. Binds with the 5'-region of CEBPB mRNA in aging liver.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded beta-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)(3) RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the beta-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family.

Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3.,Tsuda K, Kuwasako K, Takahashi M, Someya T, Inoue M, Terada T, Kobayashi N, Shirouzu M, Kigawa T, Tanaka A, Sugano S, Guntert P, Muto Y, Yokoyama S Nucleic Acids Res. 2009 Aug;37(15):5151-66. Epub 2009 Jun 24. PMID:19553194^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Timchenko NA, Welm AL, Lu X, Timchenko LT. CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoforms. Nucleic Acids Res. 1999 Nov 15;27(22):4517-25. PMID:10536163
↑ Timchenko NA, Cai ZJ, Welm AL, Reddy S, Ashizawa T, Timchenko LT. RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. J Biol Chem. 2001 Mar 16;276(11):7820-6. Epub 2000 Dec 21. PMID:11124939 doi:10.1074/jbc.M005960200
↑ Ladd AN, Charlet N, Cooper TA. The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Mol Cell Biol. 2001 Feb;21(4):1285-96. PMID:11158314 doi:10.1128/MCB.21.4.1285-1296.2001
↑ Paillard L, Legagneux V, Beverley Osborne H. A functional deadenylation assay identifies human CUG-BP as a deadenylation factor. Biol Cell. 2003 Mar-Apr;95(2):107-13. PMID:12799066
↑ Gromak N, Matlin AJ, Cooper TA, Smith CW. Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA. 2003 Apr;9(4):443-56. PMID:12649496
↑ Iakova P, Wang GL, Timchenko L, Michalak M, Pereira-Smith OM, Smith JR, Timchenko NA. Competition of CUGBP1 and calreticulin for the regulation of p21 translation determines cell fate. EMBO J. 2004 Jan 28;23(2):406-17. Epub 2004 Jan 15. PMID:14726956 doi:10.1038/sj.emboj.7600052
↑ Paul S, Dansithong W, Kim D, Rossi J, Webster NJ, Comai L, Reddy S. Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing. EMBO J. 2006 Sep 20;25(18):4271-83. Epub 2006 Aug 31. PMID:16946708 doi:10.1038/sj.emboj.7601296
↑ Moraes KC, Wilusz CJ, Wilusz J. CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA. 2006 Jun;12(6):1084-91. Epub 2006 Apr 6. PMID:16601207 doi:10.1261/rna.59606
↑ Tsuda K, Kuwasako K, Takahashi M, Someya T, Inoue M, Terada T, Kobayashi N, Shirouzu M, Kigawa T, Tanaka A, Sugano S, Guntert P, Muto Y, Yokoyama S. Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3. Nucleic Acids Res. 2009 Aug;37(15):5151-66. Epub 2009 Jun 24. PMID:19553194 doi:10.1093/nar/gkp546

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rq4"

@@ Line 1: / Line 1: @@
 ==Refinement of RNA binding domain 3 in CUG triplet repeat RNA-binding protein 1==
 <StructureSection load='2rq4' size='340' side='right' caption='[[2rq4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cpz|2cpz]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CUGBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2rq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rq4 OCA], [http://pdbe.org/2rq4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rq4 RCSB], [http://www.ebi.ac.uk/pdbsum/2rq4 PDBsum]</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=2rq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rq4 OCA], [http://pdbe.org/2rq4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rq4 RCSB], [http://www.ebi.ac.uk/pdbsum/2rq4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rq4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/2rq4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/2rq4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 47: / Line 48: @@
 [[Category: Yokoyama, S]]
 [[Category: Activator]]
+[[Category: Alternative splicing]]
+[[Category: Cytoplasm]]
 [[Category: Mrna processing]]
 [[Category: National project on protein structural and functional analyse]]

2rq4

From Proteopedia

Revision as of 08:45, 12 September 2018

Refinement of RNA binding domain 3 in CUG triplet repeat RNA-binding protein 1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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