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

Oncogene. 2000 Sep 28;19(41):4773-86. doi: 10.1038/sj.onc.1203835.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / chemistry
  • 3' Untranslated Regions / physiology*
  • 3T3 Cells
  • Animals
  • Base Pairing
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • Connective Tissue Growth Factor
  • Gene Expression Regulation*
  • Genes, Reporter
  • Genes, Synthetic
  • Growth Substances / biosynthesis
  • Growth Substances / genetics*
  • HeLa Cells
  • Humans
  • Immediate-Early Proteins / biosynthesis
  • Immediate-Early Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics*
  • Regulatory Sequences, Nucleic Acid*
  • Sequence Deletion
  • Structure-Activity Relationship


  • 3' Untranslated Regions
  • CCN2 protein, human
  • CCN2 protein, mouse
  • Growth Substances
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Connective Tissue Growth Factor