The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Fabio Henrique dos Santos
Data de Publicação: 2019
Outros Autores: Firczuk, Helena, Breeze, Alexander L., Cameron, Alexander D., Walko, Martin, Wilson, Andrew J., Zanchin, Nilson Ivo Tonin, McCarthy, John E. G.
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/34119
Resumo: Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.
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spelling Rodrigues, Fabio Henrique dos SantosFirczuk, HelenaBreeze, Alexander L.Cameron, Alexander D.Walko, MartinWilson, Andrew J.Zanchin, Nilson Ivo ToninMcCarthy, John E. G.2019-07-15T19:21:04Z2019-07-15T19:21:04Z2019RODRIGUES, Fábio Henrique dos Santos et al. The Leishmania PABP1–eIF4E4 interface: a novel 5 –3 interaction architecture for trans-spliced mRNAs. Nucleic Acids Research, v. 47, n. 3, p. 1493–1504, 2019.1362-4962https://www.arca.fiocruz.br/handle/icict/3411910.1093/nar/gky11871362-4962porOxford University PressThe Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleWarwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.Astbury Centre for Structural Molecular Biology. University of Leeds. Ledds, UK. / Faculty of Biological Sciences. University of Leeds. Leeds, UK.Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.Astbury Centre for Structural Molecular Biology. University of Leeds. Ledds, UK. / School of Chemistry. University of Leeds. Leeds, UK.Astbury Centre for Structural Molecular Biology. University of Leeds. Ledds, UK. / School of Chemistry. University of Leeds. Leeds, UK.Fundação Oswaldo Cruz. Instituto Carlos Chaga. Curitiba, PR, Brasil.Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.Trans-splicing of trypanosomatid polycistronic transcripts produces polyadenylated monocistronic mRNAs modified to form the 5' cap4 structure (m7Gpppm36,6,2'Apm2'Apm2'Cpm23,2'U). NMR and X-ray crystallography reveal that Leishmania has a unique type of N-terminally-extended cap-binding protein (eIF4E4) that binds via a PAM2 motif to PABP1. This relies on the interactions of a combination of polar and charged amino acid side-chains together with multiple hydrophobic interactions, and underpins a novel architecture in the Leishmania cap4-binding translation factor complex. Measurements using microscale thermophoresis, fluorescence anisotropy and surface plasmon resonance characterize the key interactions driving assembly of the Leishmania translation initiation complex. We demonstrate that this complex can accommodate Leishmania eIF4G3 which, unlike the standard eukaryotic initiation complex paradigm, binds tightly to eIF4E4, but not to PABP1. Thus, in Leishmania, the chain of interactions 5'cap4-eIF4E4-PABP1-poly(A) bridges the mRNA 5' and 3' ends. Exceptionally, therefore, by binding tightly to two protein ligands and to the mRNA 5' cap4 structure, the trypanosomatid N-terminally extended form of eIF4E acts as the core molecular scaffold for the mRNA-cap-binding complex. Finally, the eIF4E4 N-terminal extension is an intrinsically disordered region that transitions to a partly folded form upon binding to PABP1, whereby this interaction is not modulated by poly(A) binding to PABP1.Trans-SplicingRNA Cap-Binding ProteinsTrans-EmpalmeProteínas de Unión a Caperuzas de ARNProteínas de Ligação ao Cap de RNALeishmaniaTrypanosomatinainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/34119/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINALgky118.pdfgky118.pdfapplication/pdf4910069https://www.arca.fiocruz.br/bitstream/icict/34119/2/gky118.pdf3a8746780104a8dec5afdb002309149fMD52TEXTgky118.pdf.txtgky118.pdf.txtExtracted texttext/plain65848https://www.arca.fiocruz.br/bitstream/icict/34119/3/gky118.pdf.txte24f3eb0e6e1d9dd16bda79ce23fb626MD53icict/341192019-07-16 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dc.title.pt_BR.fl_str_mv The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
title The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
spellingShingle The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
Rodrigues, Fabio Henrique dos Santos
Trans-Splicing
RNA Cap-Binding Proteins
Trans-Empalme
Proteínas de Unión a Caperuzas de ARN
Proteínas de Ligação ao Cap de RNA
Leishmania
Trypanosomatina
title_short The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
title_full The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
title_fullStr The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
title_full_unstemmed The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
title_sort The Leishmania PABP1-eIF4E4 interface: a novel 5'-3' interaction architecture for trans-spliced mRNAs
author Rodrigues, Fabio Henrique dos Santos
author_facet Rodrigues, Fabio Henrique dos Santos
Firczuk, Helena
Breeze, Alexander L.
Cameron, Alexander D.
Walko, Martin
Wilson, Andrew J.
Zanchin, Nilson Ivo Tonin
McCarthy, John E. G.
author_role author
author2 Firczuk, Helena
Breeze, Alexander L.
Cameron, Alexander D.
Walko, Martin
Wilson, Andrew J.
Zanchin, Nilson Ivo Tonin
McCarthy, John E. G.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Rodrigues, Fabio Henrique dos Santos
Firczuk, Helena
Breeze, Alexander L.
Cameron, Alexander D.
Walko, Martin
Wilson, Andrew J.
Zanchin, Nilson Ivo Tonin
McCarthy, John E. G.
dc.subject.en.pt_BR.fl_str_mv Trans-Splicing
RNA Cap-Binding Proteins
topic Trans-Splicing
RNA Cap-Binding Proteins
Trans-Empalme
Proteínas de Unión a Caperuzas de ARN
Proteínas de Ligação ao Cap de RNA
Leishmania
Trypanosomatina
dc.subject.es.pt_BR.fl_str_mv Trans-Empalme
Proteínas de Unión a Caperuzas de ARN
Proteínas de Ligação ao Cap de RNA
dc.subject.decs.pt_BR.fl_str_mv Leishmania
Trypanosomatina
description Warwick Integrative Synthetic Biology Centre (WISB) and School of Life Sciences. University of Warwick. Gibbet Hill, UK.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-07-15T19:21:04Z
dc.date.available.fl_str_mv 2019-07-15T19:21:04Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv RODRIGUES, Fábio Henrique dos Santos et al. The Leishmania PABP1–eIF4E4 interface: a novel 5 –3 interaction architecture for trans-spliced mRNAs. Nucleic Acids Research, v. 47, n. 3, p. 1493–1504, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/34119
dc.identifier.issn.pt_BR.fl_str_mv 1362-4962
dc.identifier.doi.none.fl_str_mv 10.1093/nar/gky1187
dc.identifier.eissn.none.fl_str_mv 1362-4962
identifier_str_mv RODRIGUES, Fábio Henrique dos Santos et al. The Leishmania PABP1–eIF4E4 interface: a novel 5 –3 interaction architecture for trans-spliced mRNAs. Nucleic Acids Research, v. 47, n. 3, p. 1493–1504, 2019.
1362-4962
10.1093/nar/gky1187
url https://www.arca.fiocruz.br/handle/icict/34119
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
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