title: Regulation of translation initiation by the yeast eIF4E binding proteins is required for the pseudohyphal response.
abstract: The eukaryotic translation initiation factor eIF4E is responsible for the recognition of the mRNA cap structure and, as such, plays a key role in the selection of mRNAs for translation. The interaction of eIF4E with the 'multi-adaptor' eIF4G (and thus recruitment of ribosomes to mRNA) can be regulated via competitive binding of 4E-binding proteins (4E-BPs). 4E-BPs have broad functions in cell growth, proliferation and development. We have found that disruption of the genes for either of the yeast 4E-BPs (Eap1p or Caf20p) leads to an inhibition of pseudohyphal growth in the resulting diploid yeast strain following nitrogen limitation. Specific 4E-binding domain mutations destroy the capacity of each 4E-BP gene to complement the non-pseudohyphal phenotype, suggesting that a translational function for the 4E-BPs is important for pseudohyphal growth. In addition, neither of the 4E-BP deletion strains is deficient in global or stress-regulated protein synthesis. However, our evidence reveals that the two 4E-BPs are functionally distinct with regard to pseudohyphal growth. Therefore, this work supports a model where the yeast 4E-BPs are acting on specific mRNAs to facilitate a defined proliferative response to environmental stress in yeast.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, The Michael Smith Building, Oxford Road, Manchester, UK.
authors.forename: Salma
authors.initials: S
authors.lastname: Ibrahimo
authors.forename: Leah E A
authors.initials: LE
authors.lastname: Holmes
authors.forename: Mark P
authors.initials: MP
authors.lastname: Ashe
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D049109:Cell Proliferation; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000502:physiology*; D008969:Molecular Sequence Data; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012315:RNA Caps; D012333:RNA, Messenger / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039502:Nuclear Cap-Binding Protein Complex; D010448:Peptide Initiation Factors; D012315:RNA Caps; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C410795:eIF4E-associated protein Eap1