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

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...

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Autores: Chávez, Santiago, Eastman, Guillermo, Smircich, Pablo, Becco, Lorena, Oliveira-Rizzo, Carolina, Fort Canobra, Rafael S, Potenza, Mariana, Garat, Beatriz, Sotelo-Silveira, José Roberto, Duhagon, María Ana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Uruguay
Institución:Universidad de la República
Repositorio:COLIBRI
Idioma:inglés
OAI Identifier:oai:colibri.udelar.edu.uy:20.500.12008/22646
Acceso en línea:https://hdl.handle.net/20.500.12008/22646
Access Level:acceso abierto
Palabra clave:Trypanosoma Cruzi
Genética
ARN
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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
Genética
ARN
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
Oliveira-Rizzo, Carolina
Fort Canobra, Rafael S
Potenza, Mariana
Garat, Beatriz
Sotelo-Silveira, José Roberto
Duhagon, María Ana
author Chávez, Santiago
author_facet Chávez, Santiago
Eastman, Guillermo
Smircich, Pablo
Becco, Lorena
Oliveira-Rizzo, Carolina
Fort Canobra, Rafael S
Potenza, Mariana
Garat, Beatriz
Sotelo-Silveira, José Roberto
Duhagon, María Ana
author_role author
author2 Eastman, Guillermo
Smircich, Pablo
Becco, Lorena
Oliveira-Rizzo, Carolina
Fort Canobra, Rafael S
Potenza, Mariana
Garat, Beatriz
Sotelo-Silveira, José Roberto
Duhagon, María Ana
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.filiacion.none.fl_str_mv Chávez Santiago, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Eastman Guillermo, IIBCE
Smircich Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Becco Lorena, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Oliveira-Rizzo Carolina, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Fort Canobra Rafael S., Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Potenza M.
Garat Beatríz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Sotelo-Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
Duhagon María Ana, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología
dc.subject.es.fl_str_mv Trypanosoma Cruzi
Genética
ARN
topic Trypanosoma Cruzi
Genética
ARN
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, p0.01), 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.issued.none.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2019-12-04T13:35:05Z
dc.date.available.none.fl_str_mv 2019-12-04T13:35:05Z
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.es.fl_str_mv Chavez, S., Eastman, G., Smircich, P. y otros. "Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control". PLoS ONE [en línea]. 2017, 12 (11), art. no. e0188441. doi: 10.1371/journal.pone.0188441
dc.identifier.issn.none.fl_str_mv 1932-6203
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/22646
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0188441
identifier_str_mv Chavez, S., Eastman, G., Smircich, P. y otros. "Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control". PLoS ONE [en línea]. 2017, 12 (11), art. no. e0188441. doi: 10.1371/journal.pone.0188441
1932-6203
10.1371/journal.pone.0188441
url https://hdl.handle.net/20.500.12008/22646
dc.language.iso.none.fl_str_mv en
eng
language_invalid_str_mv en
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dc.relation.none.fl_str_mv PLoS ONE, 2017, 12 (11), art. no. e0188441
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rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
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spelling Chávez Santiago, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaEastman Guillermo, IIBCESmircich Pablo, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaBecco Lorena, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaOliveira-Rizzo Carolina, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaFort Canobra Rafael S., Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaPotenza M.Garat Beatríz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaSotelo-Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de BiologíaDuhagon María Ana, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología2019-12-04T13:35:05Z2019-12-04T13:35:05Z2017Chavez, S., Eastman, G., Smircich, P. y otros. "Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control". PLoS ONE [en línea]. 2017, 12 (11), art. no. e0188441. doi: 10.1371/journal.pone.01884411932-6203https://hdl.handle.net/20.500.12008/2264610.1371/journal.pone.0188441Trypanosoma 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, p0.01), 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.Submitted by Faget Cecilia (lfaget@fcien.edu.uy) on 2019-12-03T15:43:55Z No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0188441.pdf: 5504268 bytes, checksum: 638c4a49e45f72e99caaded2f6e67451 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2019-12-03T20:55:34Z (GMT) No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0188441.pdf: 5504268 bytes, checksum: 638c4a49e45f72e99caaded2f6e67451 (MD5)Made available in DSpace on 2019-12-04T13:35:05Z (GMT). No. of bitstreams: 2 license_rdf: 19874 bytes, checksum: 38cb62ef53e6f513db2fb7e337df6485 (MD5) 101371journalpone0188441.pdf: 5504268 bytes, checksum: 638c4a49e45f72e99caaded2f6e67451 (MD5) Previous issue date: 201727 happlication/pdfenengPLoSPLoS ONE, 2017, 12 (11), art. no. e0188441Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)Trypanosoma CruziGenéticaARNTranscriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of controlArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaChávez, SantiagoEastman, GuillermoSmircich, PabloBecco, LorenaOliveira-Rizzo, CarolinaFort Canobra, Rafael SPotenza, MarianaGarat, BeatrizSotelo-Silveira, José RobertoDuhagon, María AnaLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/22646/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; 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públicahttps://udelar.edu.uy/https://www.colibri.udelar.edu.uy/oai/requestkarina.camps@seciu.edu.uyUruguayopendoar:47712025-09-30T18:04:08COLIBRI - Universidad de la Repúblicafalse
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