Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: Similarities to retroviral RNA-protein interactions

Satoshi Kubota, Seiji Kondo, Takanori Eguchi, Takako Hattori, Tohru Nakanishi, Roger J. Pomerantz, Masaharu Takigawa

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The repressive effect of the 3'-untranslated region (3'-UTR) in human connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) mRNA on gene expression had been demonstrated in our previous study. Here, we identified a minimal RNA element in the 3'-UTR, which acts as a cis-acting element of structure-anchored repression (CAESAR). Deletion analyses of the 3'-UTR led us to minimize the element of 84 bases at the junction of the coding region and the 3'-UTR. The minimized RNA segment is predicted, and actually capable of forming a stable secondary structure in vitro. Mutational analyses disclosed a significant relationship between the predicted structure and repressive effect. The utility of CAESAR as a post-transcriptional regulatory element was represented by the fact that steady-state mRNA levels were not affected by CAESAR linked in cis, while protein levels from such a chimeric gene were markedly reduced. Of note, the CAESAR sequence exerted no effect, when it was placed upstream of the promoter. Finally, RNA gel electromobility-shift analyses demonstrated a nuclear factor that interacts with the folded CAESAR. Taken together, it was uncovered that CAESAR of ctgf is a novel post-transcriptional structured RNA regulatory element, probably acting through direct interactions with a nuclear factor as observed in retroviral RNA elements with certain proteins.

Original languageEnglish
Pages (from-to)4773-4786
Number of pages14
JournalOncogene
Volume19
Issue number41
DOIs
Publication statusPublished - Sep 28 2000

Keywords

  • 3'-UTR
  • Angiogenesis
  • CTGF
  • Chondrocyte
  • HIV-1 Rev

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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