Translational regulation of Hsp90 mRNA. AUG-proximal 5'-untranslated region elements essential for preferential heat shock translation.
Heat shock in Drosophila results in repression of most normal (non-heat shock) mRNA translation and the preferential translation of the heat shock mRNAs. The sequence elements that confer preferential translation have been localized to the 5'-untranslated region (5'-UTR) for Hsp22 and Hsp70 mRNAs (in Drosophila). Hsp90 mRNA is unique among the heat shock mRNAs in having extensive secondary structure in its 5'-UTR and being abundantly represented in the non-heat shocked cell. In this study, we show that Hsp90 mRNA translation is inefficient at normal growth temperature, and substantially activated by heat shock. Its preferential translation is not based on an IRES-mediated translation pathway, because overexpression of eIF4E-BP inhibits its translation (and the translation of Hsp70 mRNA). The ability of Hsp90 mRNA to be preferentially translated is conferred by its 5'-UTR, but, in contrast to Hsp22 and -70, is primarily influenced by nucleotides close to the AUG initiation codon. We present a model to account for Hsp90 mRNA translation, incorporating results indicating that heat shock inhibits eIF4F activity, and that Hsp90 mRNA translation is sensitive to eIF4F inactivation.
Ahmed
Ruhi
R
University of Southern California School of Pharmacy, Department of Molecular Pharmacology and Toxicology and School of Medicine, Los Angeles, California 90033, USA.
Duncan
Roger F
RF
D020121:5' Untranslated Regions; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013696:Temperature
D020121:5' Untranslated Regions; D039562:Eukaryotic Initiation Factor-4F; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger