4.8 Article

β-Catenin recognizes a specific RNA motif in the cyclooxygenase-2 mRNA 3'-UTR and interacts with HuR in colon cancer cells

Journal

NUCLEIC ACIDS RESEARCH
Volume 40, Issue 14, Pages 6863-6872

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gks331

Keywords

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Funding

  1. Ministry Of Education, Science And Technology (MEST) [2011-0018634, 2011-0006428, 2011-0002169]
  2. NRF [2011-006428]
  3. National Research Foundation of Korea [2011-0006428] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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RNA-binding proteins regulate multiple steps of RNA metabolism through both dynamic and combined binding. In addition to its crucial roles in cell adhesion and Wnt-activated transcription in cancer cells, beta-catenin regulates RNA alternative splicing and stability possibly by binding to target RNA in cells. An RNA aptamer was selected for specific binding to beta-catenin to address RNA recognition by beta-catenin more specifically. Here, we characterized the structural properties of the RNA aptamer as a model and identified a beta-catenin RNA motif. Similar RNA motif was found in cellular RNA, Cyclooxygenase-2 (COX-2) mRNA 3'-untranslated region (3'-UTR). More significantly, the C-terminal domain of beta-catenin interacted with HuR and the Armadillo repeat domain associated with RNA to form the RNA-beta-catenin-HuR complex in vitro and in cells. Furthermore, the tertiary RNA-protein complex was predominantly found in the cytoplasm of colon cancer cells; thus, it might be related to COX-2 protein level and cancer progression. Taken together, the beta-catenin RNA aptamer was valuable for deducing the cellular RNA aptamer and identifying novel and oncogenic RNA-protein networks in colon cancer cells.

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