Cap-independent translation is required for starvation-induced differentiation in yeast.
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.
Gilbert
Wendy V
WV
Department of Molecular and Cell Biology, Department of Chemistry, and Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Zhou
Kaihong
K
Butler
Tamira K
TK
Doudna
Jennifer A
JA
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
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