Structural insights into RNA recognition by the alternate-splicing regulator CUG-binding protein 1 Journal Article

   


Authors: Teplova, M.; Song, J.; Gaw, H. Y.; Teplov, A.; Patel, D. J.
Article Title: Structural insights into RNA recognition by the alternate-splicing regulator CUG-binding protein 1
Abstract: 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. © 2010 Elsevier Ltd.
Keywords: unclassified drug; binding affinity; protein motif; complex formation; protein binding; protein interaction; rna binding protein; rna; rna-binding proteins; amino acid sequence; molecular sequence data; sequence homology, amino acid; guanine; molecular recognition; substrate specificity; magnetic resonance spectroscopy; base sequence; hydrogen bond; hydrogen bonding; models, molecular; crystallography, x-ray; protein structure, tertiary; rna stability; protein structure; protein structure, secondary; nuclear magnetic resonance; rna binding; rna splicing; rna precursors; binding, competitive; cug binding protein 1; myotonic dystrophy
Journal Title: Structure
Volume: 18
Issue: 10
ISSN: 0969-2126
Publisher: Cell Press  
Date Published: 2010-10-13
Start Page: 1364
End Page: 1377
Language: English
DOI: 10.1016/j.str.2010.06.018
PUBMED: 20947024
PROVIDER: scopus
PMCID: PMC3381513
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-77957796477&partnerID=40&md5=fba2360f248f3193ef64f65da1394aab
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: STRUE" - "Source: Scopus"
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MSK Authors
  1. Dinshaw J Patel
    477 Patel
  2. Jikui Song
    7 Song
  3. Marianna Teplova
    18 Teplova
  4. Alexei Teplov
    35 Teplov
  5. Hai Yan Gaw
    2 Gaw
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