title: Cap binding-independent recruitment of eIF4E to cytoplasmic foci.
abstract: Eukaryotic translation initiation factor 4E (eIF4E) is required for cap-dependent initiation. In addition, eIF4E occurs in cytoplasmic foci such as processing bodies (PB) and stress granules (SG). We examined the role of key functional amino acid residues of eIF4E in the recruitment of this protein to cytoplasmic foci. We demonstrate that tryptophan residues required for mRNA cap recognition are not required for the recruitment of eIF4E to SG or PB. We show that a tryptophan residue required for protein-protein interactions is essential for the accumulation of eIF4E in granules. Moreover, we show, by the analysis of two Drosophila eIF4E isoforms, that the tryptophan residue is the common feature for eIF4E for the transfer of active mRNA from polysomes to other ribonucleoprotein particles in the cytoplasm. This residue resides in a putative interaction domain different than the eIF4E-BP domain. We conclude that protein-protein interactions rather than interactions with the mRNA are essential for the recruitment of eIF4E and for a putative nucleation function.
authors.affiliation: Laboratorio de Genética y Genómica Funcional, Centro Regional de Estudios Genómicos, Universidad Nacional de La Plata, Florencio Varela, Argentina.
authors.forename: Paola V
authors.initials: PV
authors.lastname: Ferrero
authors.forename: Carla
authors.initials: C
authors.lastname: Layana
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Paulucci
authors.forename: Pablo
authors.initials: P
authors.lastname: Gutiérrez
authors.forename: Greco
authors.initials: G
authors.lastname: Hernández
authors.forename: Rolando V
authors.initials: RV
authors.lastname: Rivera-Pomar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D012315:RNA Caps / Q000187:drug effects / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D020033:Protein Isoforms; D012315:RNA Caps; C531248:eIF4E1 protein, Drosophila; D014364:Tryptophan; D003513:Cycloheximide