| Structural highlights
3nnh is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 3nmr, 3nna, 3nnc |
| Gene: | BRUNOL2, CELF1, CUGBP, CUGBP1, NAB50 (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]
Publication Abstract from PubMed
CUG-binding protein 1 (CUGBP1) regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of myotonic dystrophy. CUGBP1 harbors three RRM domains and preferentially targets UGU-rich mRNA elements. We describe crystal structures of CUGBP1 RRM1 and tandem RRM1/2 domains bound to RNAs containing tandem UGU(U/G) elements. Both RRM1 in RRM1-RNA and RRM2 in RRM1/2-RNA complexes use similar principles to target UGU(U/G) elements, with recognition mediated by face-to-edge stacking and water-mediated hydrogen-bonding networks. The UG step adopts a left-handed Z-RNA conformation, with the syn guanine recognized through Hoogsteen edge-protein backbone hydrogen-bonding interactions. NMR studies on the RRM1/2-RNA complex establish that both RRM domains target tandem UGUU motifs in solution, whereas filter-binding assays identify a preference for recognition of GU over AU or GC steps. We discuss the implications of CUGBP1-mediated targeting and sequestration of UGU(U/G) elements on pre-mRNA alternative-splicing regulation, translational regulation, and mRNA decay.
Structural insights into RNA recognition by the alternate-splicing regulator CUG-binding protein 1.,Teplova M, Song J, Gaw HY, Teplov A, Patel DJ Structure. 2010 Oct 13;18(10):1364-77. PMID:20947024[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
- ↑ Teplova M, Song J, Gaw HY, Teplov A, Patel DJ. Structural insights into RNA recognition by the alternate-splicing regulator CUG-binding protein 1. Structure. 2010 Oct 13;18(10):1364-77. PMID:20947024 doi:10.1016/j.str.2010.06.018
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