Authors:
Irina A. Vlasova, Nuzha M. Tahoe, Danhua Fan, Ola Larsson, Bernd Rattenbacher, Julius R. SternJohn, Jayprakash Vasdewani, George Karypis, Cavan S. Reilly, Peter B. Bitterman, and Paul R. Bohjanen
Summary:
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 β-globin transcript conferred instability on the otherwise stable β-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.
Source:
Molecular Cell, Vol. 29, 263-270, 01 February 2008