title: The eIF4E subunits of two distinct trypanosomatid eIF4F complexes are subjected to differential post-translational modifications associated to distinct growth phases in culture.
abstract: The eukaryotic eIF4F complex, the cap binding complex, functions during translation initiation through interactions mediated by its three subunits (eIF4E, eIF4G and eIF4A), other initiation factors and the ribosome. In trypanosomatids, various eIF4E and eIF4G homologues were identified, with two eIF4F-like complexes confirmed (EIF4E4/EIF4G3/EIF4AI and EIF4E3/EIF4G4/EIF4AI). Here, the expression pattern of these complexes was investigated during Leishmania amazonensis and Trypanosoma brucei growth. The two sets of eIF4E and eIF4G homologues were found represented by phosphorylated isoforms with multiple phosphorylation events targeting the two eIF4E homologues. Expression of these multiple isoforms was differentially affected by inhibitors of mRNA synthesis/processing and translation. Phosphorylated EIF4E4 was consistently associated with early/active growth phases in both organisms studied. In T. brucei phosphorylation of both EIF4E3 and 4, overexpressed as HA-tagged fusions, was partially mapped to their N-terminuses. Our results indicate that phosphorylation is associated with a further layer of complexity in translation initiation in trypanosomatids.
authors.affiliation: Centro de Pesquisas Aggeu Magalhães/Fiocruz, Campus UFPE, Recife, PE 50670-420, Brazil.
authors.forename: Mariana M C
authors.initials: MM
authors.lastname: Pereira
authors.forename: Amaranta M
authors.initials: AM
authors.lastname: Malvezzi
authors.forename: Larissa M
authors.initials: LM
authors.lastname: Nascimento
authors.forename: Tamara D C da Costa
authors.initials: TD
authors.lastname: Lima
authors.forename: Viviane S
authors.initials: VS
authors.lastname: Alves
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Palma
authors.forename: Eden R
authors.initials: ER
authors.lastname: Freire
authors.forename: Danielle M N
authors.initials: DM
authors.lastname: Moura
authors.forename: Christian R S
authors.initials: CR
authors.lastname: Reis
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: de Melo Neto
mesh_terms: D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D020869:Gene Expression Profiling; D007891:Leishmania / Q000201:enzymology* / Q000254:growth & development*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000254:growth & development*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D020033:Protein Isoforms; D021122:Protein Subunits
keywords: Initiation; Phosphorylation; Protein synthesis; Regulation