Cap-Independent Translation Is Required for Starvation-Induced Differentiation in Yeast
Abstract
Cellular internal ribosome entry sites (IRESs) are untranslated segments of mRNA transcripts thought to initiate protein synthesis in response to environmental stresses that prevent canonical 5′ cap–dependent translation. Although numerous cellular mRNAs are proposed to have IRESs, none has a demonstrated physiological function or molecular mechanism. Here we show that seven yeast genes required for invasive growth, a developmental pathway induced by nutrient limitation, contain potent IRESs that require the initiation factor eIF4G for cap-independent translation. In contrast to the RNA structure-based activity of viral IRESs, we show that an unstructured A-rich element mediates internal initiation via recruitment of the poly(A) binding protein (Pab1) to the 5′ untranslated region (UTR) of invasive growth messages. A 5′UTR mutation that impairs IRES activity compromises invasive growth, which indicates that cap-independent translation is required for physiological adaptation to stress.
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We thank M. Hentze, R. Wickner, and H. Madhani for generously providing plasmids and yeast strains; M. Swanson for providing antibodies; M. Bergkessel and B. Zuchero of the Thurn and Bicycles courier service; and members of the Doudna laboratory for helpful discussions. J.A.D. is a Howard Hughes Medical Institute Investigator. W.V.G. is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-1842-04).
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Published In
Science
Volume 317 | Issue 5842
31 August 2007
31 August 2007
Copyright
American Association for the Advancement of Science.
Submission history
Received: 30 April 2007
Accepted: 20 July 2007
Published in print: 31 August 2007
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