title: 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.
authors.affiliation: Department of Molecular and Cell Biology, Department of Chemistry, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
authors.forename: Wendy V
authors.initials: WV
authors.lastname: Gilbert
authors.forename: Kaihong
authors.initials: K
authors.lastname: Zhou
authors.forename: Tamira K
authors.initials: TK
authors.lastname: Butler
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doudna
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000222:Adaptation, Physiological; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D005947:Glucose / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D011061:Poly A / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D039603:Eukaryotic Initiation Factor-4G; C100940:FLO8 protein, S cerevisaie; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D012315:RNA Caps; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C450100:pab1 protein, S cerevisiae; D011061:Poly A; D005947:Glucose