Upstream open reading frames regulate the translation of the multiple mRNA variants of the estrogen receptor alpha.
It is by now well established that the estrogen receptor alpha (ER alpha) 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 alpha contain between one and six upstream open reading frames. In this study the effect of the 5'-UTRs of major human and mouse ER alpha 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 alpha mRNAs have the potential to regulate estrogen receptor alpha expression.
Kos
Martin
M
European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Denger
Stefanie
S
Reid
George
G
Gannon
Frank
F
D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D047628:Estrogen Receptor alpha; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D003062:Codon; D017931:DNA Primers; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen