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Wendy V. Gilbert
Translation initiation is a crucial point of regulation of eukaryotic
gene expression. A wide variety of environmental insults, including
starvation, irradiation, and oxidative stress, inhibit the primary
mechanism for translation of most messages, while favoring expression
of a select group of genes by an alternative initiation mechanism using
internal ribosome entry sites (IRESs). Many proposed cellular IRESs
occur in stress-responsive transcription factors, including two AP-1
family members, the vertebrate oncogene c-Jun and yeast YAP1. While
much has been discovered about the diverse mechanisms of translation
initiation mediated by viral IRESs, no mechanism of initiation mediated
by any cellular IRES has yet been elucidated.
The goal of my work is to understand the molecular mechanisms responsible
for translation initiation by the yeast YAP1 IRES, and to explore
the intriguing possibility that regulated IRES-dependent translation
contributes to cell survival under conditions of environmental stress.
Ultimately, I hope to solve the structure of the active YAP1 IRES, and
determine how this structure interacts with the translational machinery
to promote cap-independent initiation.
Selected Publications
Gilbert, W.V., Zhou, K., Butler, T.K. and Doudna, J.A. (2007)
Cap-independent translation is required for starvation-induced differentiation in yeast.
Science 317, 1224-1227.
(380KB .pdf)
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