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

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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Vlasova IA,Tahoe NM,Fan D,Larsson O,Rattenbacher B,Sternjohn JR,Vasdewani J,Karypis G,Reilly CS,Bitterman PB,Bohjanen PR

doi

10.1016/j.molcel.2007.11.024

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

263-70

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(07)00819-2

journal_volume

29

pub_type

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