Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1

Mol Cell. 2008 Feb 1;29(2):263-70. doi: 10.1016/j.molcel.2007.11.024.


We used computational algorithms to find conserved sequences in the 3' untranslated region (UTR) of transcripts that exhibited rapid decay in primary human T cells and found that the consensus sequence UGUUUGUUUGU, which we have termed a GU-rich element (GRE), was enriched in short-lived transcripts. Using a tet-off reporter system, we showed that insertion of GRE-containing sequences from c-jun, jun B, or TNF receptor 1B, but not mutated GRE sequences, into the 3'UTR of a beta-globin transcript conferred instability on the otherwise stable beta-globin transcript. CUG-binding protein 1 (CUGBP1) was identified as the major GRE-binding activity in cytoplasmic extracts from primary human T cells based on supershift and immunoprecipitation assays. siRNA-mediated knockdown of CUGBP1 in HeLa cells caused stabilization of GRE-containing transcripts, suggesting that CUGBP1 is a mediator of GRE-dependent mRNA decay. Overall, our results suggest that the GRE mediates coordinated mRNA decay by binding to CUGBP1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism*
  • CELF1 Protein
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Globins / genetics
  • Globins / metabolism
  • HeLa Cells
  • Humans
  • Protein Binding / physiology
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA Stability / physiology*
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*


  • 3' Untranslated Regions
  • CELF1 Protein
  • CELF1 protein, human
  • Proto-Oncogene Proteins c-jun
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Receptors, Tumor Necrosis Factor
  • Globins