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

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

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1
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

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.

PMID:
18243120
PMCID:
PMC2367162
DOI:
10.1016/j.molcel.2007.11.024
[Indexed for MEDLINE]
Free PMC Article

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