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J. Biol. Chem., Vol. 277, Issue 40, 37131-37138, October 4, 2002
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From the European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
It is by now well established that the estrogen
receptor
Upstream Open Reading Frames Regulate the Translation of the
Multiple mRNA Variants of the Estrogen Receptor
*
,
(ER) is transcribed from multiple promoters. One direct
consequence of multiple promoters is the generation of mRNA
variants with different 5'-untranslated regions (5'-UTRs).
However, the potential roles of these individual mRNA variants are
not known. All 5'-UTRs of ER contain between one and six upstream
open reading frames. In this study the effect of the 5'-UTRs of major
human and mouse ER mRNA variants on translation was evaluated.
Some of the 5'-UTRs were found to strongly inhibit translation of the
downstream open reading frame. Mutation of the upstream AUG codons
partially or completely restored translation efficiency. A toeprinting
analysis and assessment of the contribution of each AUG codon to the
inhibitory effect on translation showed that leaky scanning and
reinitiation occurs with these mRNAs. In conclusion, the upstream
open reading frames in the 5'-UTRs of ER mRNAs have the
potential to regulate estrogen receptor expression.
*
This work was supported in part by European Community Grant
QLK6-1999-02108.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: European Molecular
Biology Organization, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Tel.: 49-6221-8891102; Fax: 49-6221-8891200; E-mail: Frank.
Gannon{at}embo.org.
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