Functional characterization of three leishmania poly(a) binding protein homologues with distinct binding properties to RNA and protein partners

dc.creatorLima, Tamara D. da Costa
dc.creatorMoura, Danielle M. N.
dc.creatorReis, Christian R. S.
dc.creatorVasconcelos, J. Ronnie C.
dc.creatorEllis, Louise
dc.creatorCarrington, Mark
dc.creatorFigueiredo, Regina C. B. Q.
dc.creatorMelo Neto, Osvaldo P. de
dc.date2018-04-27T12:06:31Z
dc.date2018-04-27T12:06:31Z
dc.date2010
dc.date.accessioned2023-09-26T20:29:50Z
dc.date.available2023-09-26T20:29:50Z
dc.identifierDA COSTA LIMA, T. D. et al. Functional characterization of three leishmania poly(a) binding protein homologues with distinct binding properties to RNA and protein partners. Eukaryotic Cell, v. 9, n. 10, p. 1484–1494, out. 2010.
dc.identifier1535-9786
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/26166
dc.identifier10.1128/EC.00148-10
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8858194
dc.descriptionEste trabalho foi parcialmente financiado por subsídios fornecidos pelas agências de fomento brasileiras FACEPE ( 006/2003-CNPq / PPP ) e CNPq ( 476255 / 2004-0 ). O TDDCL, o DMNM e o CRSR receberam bolsas de estudo da CAPES e FACEPE. O JRCV recebeu uma bolsa PQ (“pesquisador visitante”) da FIOCRUZ. O trabalho no laboratório de M. Carrington é financiado pelo Wellcome Trust, e LE recebeu uma bolsa de estudos financiada pelo BBSRC.
dc.descriptionTrypanosomatid protozoans are reliant on posttranscriptional processes to control gene expression. Regulation occurs at the levels of mRNA processing, stability, and translation, events that may require the participation of the poly(A) binding protein (PABP). Here, we have undertaken a functional study of the three distinct Leishmania major PABP (LmPABP) homologues: the previously described LmPABP1; LmPABP2, orthologous to the PABP described from Trypanosoma species; and LmPABP3, unique to Leishmania. Sequence identity between the three PABPs is no greater than 40%. In assays measuring binding to A-rich sequences, LmPABP1 binding was poly(A) sensitive but heparin insensitive; LmPABP2 binding was heparin sensitive and less sensitive to poly(A), compatible with unique substitutions observed in residues implicated in poly(A) binding; and LmPABP3 displayed intermediate properties. All three homologues are simultaneously expressed as abundant cytoplasmic proteins in L. major promastigotes, but only LmPABP1 is present as multiple isoforms. Upon transcription inhibition, LmPABP2 and -3 migrated to the nucleus, while LmPABP1 remained predominantly cytoplasmic. Immunoprecipitation assays showed an association between LmPABP2 and -3. Although the three proteins bound to a Leishmania homologue of the translation initiation factor eukaryotic initiation factor 4G (eIF4G) (LmEIF4G3) in vitro, LmPABP1 was the only one to copurify with native LmEIF4G3 from cytoplasmic extracts. Functionality was tested using RNA interference (RNAi) in Trypanosoma brucei, where both orthologues to LmPABP1 and -2 are required for cellular viability. Our results indicate that these homologues have evolved divergent functions, some of which may be unique to the trypanosomatids, and reinforces a role for LmPABP1 in translation through its interaction with the eIF4G homologue.
dc.formatapplication/pdf
dc.languageeng
dc.rightsopen access
dc.subjectLeishmania
dc.subjectRNA
dc.subjectTrypanosoma brucei
dc.subjecteIF4G
dc.subjectLeishmania
dc.subjectRNA
dc.subjectTrypanosoma brucei
dc.subjecteIF4G
dc.subjectSequência de Aminoácidos
dc.subjectAnimais
dc.subjectEncadernação
dc.subjectSobrevivência Celular
dc.subjectFator de iniciação eucariótica-4G / metabolismo
dc.subjectLeishmania major / genética
dc.subjectLeishmania major / crescimento e desenvolvimento
dc.subjectLeishmania major / metabolismo
dc.subjectDados de Sequencia Molecular
dc.subjectPoly A / metabolismo
dc.subjectProteínas de Ligação Poli (A) / química
dc.subjectProteínas de Ligação Poli (A) / genética
dc.subjectProteínas de Ligação Poli (A) / metabolismo
dc.subjectLigação proteica
dc.subjectBiossíntese de Proteínas
dc.subjectInterferência de RNA
dc.subjectRNA mensageiro / metabolismo
dc.subjectHomologia de Sequência, Aminoácidos
dc.subjectTrypanosoma brucei brucei / genética
dc.subjectTrypanosoma brucei brucei / metabolismo
dc.titleFunctional characterization of three leishmania poly(a) binding protein homologues with distinct binding properties to RNA and protein partners
dc.typeArticle


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