Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control

Autores
Chávez, Santiago; Eastman, Guillermo; Smircich, Pablo; Becco, Lorena Lourdes; Oliveira Rizzo, Carolina; Fort, Rafael; Potenza, Mariana; Garat, Beatriz; Sotelo Silveira, Jos¨¦ Roberto; Duhagon, María Ana
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01), coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of their gene expression control.
Fil: Chávez, Santiago. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Eastman, Guillermo. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Smircich, Pablo. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Becco, Lorena Lourdes. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Oliveira Rizzo, Carolina. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Fort, Rafael. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Potenza, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Garat, Beatriz. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Sotelo Silveira, Jos¨¦ Roberto. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Duhagon, María Ana. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Materia
TRYPANOSOMA CRUZI
CELL CICLE
TRNASCRIPTOME
PARASITOLOGY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/41426
Acceder
id CONICETDig_e1d16624a2738f06910045b498b96e15
oai_identifier_str oai:ri.conicet.gov.ar:11336/41426
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of controlChávez, SantiagoEastman, GuillermoSmircich, PabloBecco, Lorena LourdesOliveira Rizzo, CarolinaFort, RafaelPotenza, MarianaGarat, BeatrizSotelo Silveira, Jos¨¦ RobertoDuhagon, María AnaTRYPANOSOMA CRUZICELL CICLETRNASCRIPTOMEPARASITOLOGYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01), coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of their gene expression control.Fil: Chávez, Santiago. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Eastman, Guillermo. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Smircich, Pablo. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Becco, Lorena Lourdes. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Oliveira Rizzo, Carolina. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Fort, Rafael. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Potenza, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Garat, Beatriz. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Sotelo Silveira, Jos¨¦ Roberto. Universidad del Uruguay. Facultad de Ciencias; UruguayFil: Duhagon, María Ana. Universidad del Uruguay. Facultad de Ciencias; UruguayPublic Library of Science2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41426Chávez, Santiago; Eastman, Guillermo; Smircich, Pablo; Becco, Lorena Lourdes; Oliveira Rizzo, Carolina; et al.; Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control; Public Library of Science; Plos One; 12; 11; 11-2017; 1-27; e01884411932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188441info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0188441info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:45:05Zoai:ri.conicet.gov.ar:11336/41426instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:45:05.762CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
title Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
spellingShingle Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
Chávez, Santiago
TRYPANOSOMA CRUZI
CELL CICLE
TRNASCRIPTOME
PARASITOLOGY
title_short Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
title_full Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
title_fullStr Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
title_full_unstemmed Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
title_sort Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control
dc.creator.none.fl_str_mv Chávez, Santiago
Eastman, Guillermo
Smircich, Pablo
Becco, Lorena Lourdes
Oliveira Rizzo, Carolina
Fort, Rafael
Potenza, Mariana
Garat, Beatriz
Sotelo Silveira, Jos¨¦ Roberto
Duhagon, María Ana
author Chávez, Santiago
author_facet Chávez, Santiago
Eastman, Guillermo
Smircich, Pablo
Becco, Lorena Lourdes
Oliveira Rizzo, Carolina
Fort, Rafael
Potenza, Mariana
Garat, Beatriz
Sotelo Silveira, Jos¨¦ Roberto
Duhagon, María Ana
author_role author
author2 Eastman, Guillermo
Smircich, Pablo
Becco, Lorena Lourdes
Oliveira Rizzo, Carolina
Fort, Rafael
Potenza, Mariana
Garat, Beatriz
Sotelo Silveira, Jos¨¦ Roberto
Duhagon, María Ana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
CELL CICLE
TRNASCRIPTOME
PARASITOLOGY
topic TRYPANOSOMA CRUZI
CELL CICLE
TRNASCRIPTOME
PARASITOLOGY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01), coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of their gene expression control.
Fil: Chávez, Santiago. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Eastman, Guillermo. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Smircich, Pablo. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Becco, Lorena Lourdes. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Oliveira Rizzo, Carolina. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Fort, Rafael. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Potenza, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
Fil: Garat, Beatriz. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Sotelo Silveira, Jos¨¦ Roberto. Universidad del Uruguay. Facultad de Ciencias; Uruguay
Fil: Duhagon, María Ana. Universidad del Uruguay. Facultad de Ciencias; Uruguay
description Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01), coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of their gene expression control.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/41426
Chávez, Santiago; Eastman, Guillermo; Smircich, Pablo; Becco, Lorena Lourdes; Oliveira Rizzo, Carolina; et al.; Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control; Public Library of Science; Plos One; 12; 11; 11-2017; 1-27; e0188441
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41426
identifier_str_mv Chávez, Santiago; Eastman, Guillermo; Smircich, Pablo; Becco, Lorena Lourdes; Oliveira Rizzo, Carolina; et al.; Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control; Public Library of Science; Plos One; 12; 11; 11-2017; 1-27; e0188441
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188441
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0188441
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083551732170752
score 13.22299

Publicaciones similares