Rapamycin conditionally inhibits Hsp90 but not Hsp70 mRNA translation in <Emphasis Type="Italic">Drosophila</Emphasis>: implications for the mechanisms of Hsp mRNA translation |
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Authors: | Roger F Duncan |
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Institution: | (1) Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA, USA;(2) Department of Molecular Microbiology and Immunology, School of Medicine, University of Southern California School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90033, USA |
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Abstract: | Rapamycin inhibits the activity of the target of rapamycin (TOR)-dependent signaling pathway, which has been characterized
as one dedicated to translational regulation through modulating cap-dependent translation, involving eIF4E binding protein
(eIF4E-BP) or 4E-BP. Results show that rapamycin strongly inhibits global translation in Drosophila cells. However, Hsp70 mRNA translation is virtually unaffected by rapamycin treatment, whereas Hsp90 mRNA translation is
strongly inhibited, at normal growth temperature. Intriguingly, during heat shock Hsp90 mRNA becomes significantly less sensitive
to rapamycin-mediated inhibition, suggesting the pathway for Hsp90 mRNA translation is altered during heat shock. Reporter
mRNAs containing the Hsp90 or Hsp70 mRNAs’ 5′ untranslated region recapitulate these rapamycin-dependent translational characteristics,
indicating this region regulates rapamycin-dependent translational sensitivity as well as heat shock preferential translation.
Surprisingly, rapamycin-mediated inhibition of Hsp90 mRNA translation at normal growth temperature is not caused by 4E-BP-mediated
inhibition of cap-dependent translation. Indeed, no evidence for rapamycin-mediated impaired eIF4E function is observed. These
results support the proposal that preferential translation of different Hsp mRNA utilizes distinct translation mechanisms,
even within a single species. |
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Keywords: | Translation Heat shock Rapamycin Hsp90 Hsp70 |
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