The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation

dc.creatorde Melo Neto, Osvaldo P.
dc.creatorda Costa Lima, Tamara D. C.
dc.creatorXavier, Camila C.
dc.creatorNascimento, Larissa M.
dc.creatorRomão, Tatiany P.
dc.creatorAssis, Ludmila A.
dc.creatorPereira, Mariana M. C.
dc.creatorReis, Christian R. S.
dc.creatorPapadopoulou, Barbara
dc.date2017-09-20T18:07:37Z
dc.date2017-09-20T18:07:37Z
dc.date2015
dc.date.accessioned2023-09-26T20:45:55Z
dc.date.available2023-09-26T20:45:55Z
dc.identifierDE MELO NETO, O. P. et al. The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation. RNA biology, v. 12, n. 11, p. 1209–1221, 2015.
dc.identifier1555-8584
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/21075
dc.identifier10.1080/15476286.2015.1086865
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8863473
dc.descriptionThe eukaryotic initiation factor 4E (eIF4E) recognizes the mRNA cap structure and, together with eIF4G and eIF4A, form the eIF4F complex that regulates translation initiation in eukaryotes. In trypanosomatids, 2 eIF4E homologues (EIF4E3 and EIF4E4) have been shown to be part of eIF4F-like complexes with presumed roles in translation initiation. Both proteins possess unique N-terminal extensions, which can be targeted for phosphorylation. Here, we provide novel insights on the Leishmania infantum EIF4E4 function and regulation. We show that EIF4E4 is constitutively expressed throughout the parasite development but is preferentially phosphorylated in exponentially grown promastigote and amastigote life stages, hence correlating with high levels of translation. Phosphorylation targets multiple serine-proline or threonine-proline residues within the N-terminal extension of EIF4E4 but does not require binding to the EIF4E4's partner, EIF4G3, or to the cap structure. We also report that EIF4E4 interacts with PABP1 through 3 conserved boxes at the EIF4E4 N-terminus and that this interaction is a prerequisite for efficient EIF4E4 phosphorylation. EIF4E4 is essential for Leishmania growth and an EIF4E4 null mutant was only obtained in the presence of an ectopically provided wild type gene. Complementation for the loss of EIF4E4 with several EIF4E4 mutant proteins affecting either phosphorylation or binding to mRNA or to EIF4E4 protein partners revealed that, in contrast to other eukaryotes, only the EIF4E4-PABP1 interaction but neither the binding to EIF4G3 nor phosphorylation is essential for translation. These studies also demonstrated that the lack of both EIF4E4 phosphorylation and EIF4G3 binding leads to a non-functional protein. Altogether, these findings further highlight the unique features of the translation initiation process in trypanosomatid protozoa.
dc.formatapplication/pdf
dc.languagepor
dc.rightsopen access
dc.subjectFator de Iniciação 4E em Eucariotos
dc.subjectLeishmania
dc.subjectIniciação Traducional da Cadeia Peptídica
dc.subjectDomínios e Motivos de Interação entre Proteínas
dc.subjectAmino Acid Motifs
dc.subjectAmino Acid Sequence
dc.subjectcap binding protein
dc.subjectConserved Sequence
dc.subjecteIF4E
dc.subjecteIF4G
dc.subjectEukaryotic Initiation Factor-4E
dc.subjectEukaryotic Initiation Factor-4G
dc.subjectGene Expression
dc.subjectGene Knockout Techniques
dc.subjectLeishmania
dc.subjectLife Cycle Stages
dc.subjectMolecular Sequence Data
dc.subjectPeptide Chain Initiation, Translational
dc.subjectPhosphorylation
dc.subjectPoly(A)-Binding Proteins
dc.subjectProtein Binding
dc.subjectProtein Interaction Domains and Motifs
dc.subjectprotein synthesis
dc.subjectSequence Alignment
dc.subjecttranslation initiation PABP
dc.subjectFator de Iniciação 4E em Eucariotos
dc.subjectLeishmania
dc.subjectgenética
dc.subjectmetabolismo
dc.subjectcrescimento & desenvolvimento
dc.subjectDomínios e Motivos de Interação entre Proteínas
dc.subjectIniciação Traducional da Cadeia Peptídica
dc.subjectMotivos de Aminoácidos
dc.subjectSequência de Aminoácidos
dc.subjectSequência Conservada
dc.subjectExpressão Gênica
dc.subjectTécnicas de Inativação de Genes
dc.subjectEstágios do Ciclo de Vida
dc.subjectDados de Sequência Molecular
dc.subjectFosforilação
dc.subjectProteínas de Ligação a Poli(A)
dc.subjectLigação Proteica
dc.subjectAlinhamento de Sequência
dc.titleThe unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation
dc.typeArticle


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