Publication Date:
2007-09-01
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Wendy V -- Zhou, Kaihong -- Butler, Tamira K -- Doudna, Jennifer A -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1224-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Department of Chemistry, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761883" target="_blank"〉PubMed〈/a〉
Keywords:
*5' Untranslated Regions/genetics/metabolism
;
Adaptation, Physiological
;
Eukaryotic Initiation Factor-4G/genetics/metabolism
;
Genes, Fungal
;
Glucose/metabolism
;
Nuclear Proteins/biosynthesis/genetics/metabolism
;
Nucleic Acid Conformation
;
*Peptide Chain Initiation, Translational
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Poly A/metabolism
;
Poly(A)-Binding Proteins/metabolism
;
Protein Biosynthesis
;
RNA Caps/metabolism
;
RNA, Fungal/chemistry/*genetics/metabolism
;
RNA, Messenger/chemistry/*genetics/metabolism
;
Saccharomyces cerevisiae/*genetics/*growth & development/metabolism
;
Saccharomyces cerevisiae Proteins/biosynthesis/genetics/metabolism
;
Trans-Activators/biosynthesis/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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