Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30033
Title: An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway
Authors: Serpeloni, Mariana
Moraes, Carolina Borsoi
Muniz, João Renato Carvalho
Motta, Maria Cristina Machado
Ramos, Augusto Savio Peixoto
Kessler, Rafael Luis
Inoue, Alexandre Haruo
Rocha, Wanderson Duarte da
Yamada-Ogatta, Sueli Fumie
Fragoso, Stenio Perdigão
Goldenberg, Samuel
Freitas-Junior, Lucio H.
Ávila, Andréa Rodrigues
Affilliation: Universidade Federal do Paraná. Departamento de Biologia Celular e Molecular. Curitiba, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Gyeonggi-do, South Korea.
University of Oxford. Oxford. United Kingdom.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Departamento de Biologia Celular e Parasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Universidade Federal do Paraná. Departamento de Biologia Celular e Molecular. Curitiba, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Universidade Federal do Paraná. Departamento de Biologia Celular e Molecular. Curitiba, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Universidade Federal do Paraná. Departamento de Bioquímica. Curitiba, PR, Brasil.
Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Microbiologia. Londrina, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Gyeonggi-do, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Regulação da Expressão Gênica. Curitiba, PR, Brasil.
Abstract: In eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX) multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II), but not RNA polymerase I (RNA pol I) or Spliced Leader (SL) transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and decrease of translation levels, reinforcing that Trypanosoma-Sub2 (Tryp-Sub2) is a component of mRNA transcription/export pathway in trypanosomes.
Keywords: RNA, Messenger
Transcription Genetic
Gene Expression
Keywords in spanish: ARN Mensajero
Transcripción Genética
Expresión Génica
DeCS: RNA Mensageiro
Trypanosoma cruzi
Transcrição Genética
Trypanosoma
Expressão Gênica
Issue Date: 2011
Publisher: Public Library of Science
Citation: SERPELONI, Mariana et al. An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway. PLoS ONE, v. 6, n. 6, p. 1-14, 2011.
DOI: 10.1371/journal.pone.0020730
ISSN: 1932-6203
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos

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