title: Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila.
abstract: The Drosophila genome-sequencing project has revealed a total of seven genes encoding eight eukaryotic initiation factor 4E (eIF4E) isoforms. Four of them (eIF4E-1,2, eIF4E-3, eIF4E-4 and eIF4E-5) share exon/intron structure in their carboxy-terminal part and form a cluster in the genome. All eIF4E isoforms bind to the cap (m7GpppN) structure. All of them, except eIF4E-6 and eIF4E-8 were able to interact with Drosophila eIF4G or eIF4E-binding protein (4E-BP). eIF4E-1, eIF4E-2, eIF4E-3, eIF4E-4 and eIF4E-7 rescued a yeast eIF4E-deficient mutant in vivo. Only eIF4E-1 mRNAs and, at a significantly lower level, eIF4E3 and eIF4E-8 are expressed in embryos and throughout the life cycle of the fly. The transcripts of the remaining isoforms were detected from the third instar larvae onwards. This indicates the cap-binding activity relies mostly on eIF4E-1 during embryogenesis. This agrees with the proteomic analysis of the eIF4F complex purified from embryos and with the rescue of l(3)67Af, an embryonic lethal mutant for the eIF4E-1,2 gene, by transgenic expression of eIF4E-1. Overexpression of eIF4E-1 in wild-type embryos and eye imaginal discs results in phenotypic defects in a dose-dependent manner.
authors.affiliation: Max-Planck-Institut für biophysikalische Chemie, Abt. Molekulare Biologie, Am Fassberg 11, Göttingen 37077, Germany. hgreco@gwdg.de
authors.forename: Greco
authors.initials: G
authors.lastname: Hernández
authors.forename: Michael
authors.initials: M
authors.lastname: Altmann
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Sierra
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Ruth
authors.initials: R
authors.lastname: Diez del Corral
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Rolando
authors.initials: R
authors.lastname: Rivera-Pomar
mesh_terms: D000375:Aging / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005123:Eye / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D016415:Sequence Alignment
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D020033:Protein Isoforms