A long noncoding RNA promotes parasite differentiation in African trypanosomes

Detalhes bibliográficos
Autor(a) principal: Guegan, Fabien Marc
Data de Publicação: 2022
Outros Autores: Rajan, K. Shanmugha, Bento, Fabio, Neves, Daniel, Sequeira, Mariana, Gumińska, Natalia, Mroczek, Seweryn, Dziembowski, Andrzej, Cohen-Chalamish, Smadar, Doniger, Tirza, Galili, Beathrice, Estévez, Antonio M., Notredame, Cedric, Michaeli, Shulamit, Figueiredo, Luisa M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/53851
Resumo: Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)
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spelling A long noncoding RNA promotes parasite differentiation in African trypanosomesCopyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we used RNA sequencing to survey the T. brucei genome, identifying 1428 previously uncharacterized lncRNA genes. We find that grumpy lncRNA is a key regulator that promotes parasite differentiation into the quiescent stumpy form. This function is promoted by a small nucleolar RNA encoded within the grumpy lncRNA. snoGRUMPY binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. grumpy overexpression reduces parasitemia in infected mice. Our analyses suggest that T. brucei lncRNAs modulate parasite-host interactions and provide a mechanism by which grumpy regulates cell differentiation in trypanosomes.This work was supported in part by Fundação para a Ciência e Tecnologia (FCT) grant, awarded to F.G. and entitled “Long noncoding RNAs as new diagnostic biomarkers for African Sleeping sickness” (PTDC/DTPEPI/7099/2014, start date: 1 January 2016, end date: 31 December 2018); also by Howard Hughes Medical Institute International Early Career Scientist Program (project title: “How parasites use epigenetics to evade host defenses,” project no. 55007419, start date: 1 February 2012, end date: 31 January 2017); and by the European Research Council (project title: “Exploring the hidden life of African trypanosomes: parasite fat tropism and implications for the disease,” project no. 771714, start date: 1 August 2018, end date: 31 January 2024), both awarded to L.M.F. The project leading to these results have received funding from “la Caixa” Foundation under the agreement LCF/PR/HR20/52400019 [project title: “Mechanism and function of epitranscriptomic poly(A) tail modifications in African trypanosomes,” project no. HR20-00361, start date: 1 March 2021, end date: 29 February 2024]. L.M.F. is supported by FCT (IF/01050/2014, project title: “Molecular basis for the efficient biology of trypanossome parasitism,” start date: 1 January 2015, end date: 31 December 2019) and by CEEC institutional program (CEECINST/00110/2018, start date: 1 January 2020, end date: 14 December 2020). C.N. acknowledges the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya. S. Michaeli acknowledges the support of the Israel Science Foundation (ref. 1959/20) from October 2020 to October 2025, entitled “Functional analysis of rRNA processing and the role of rRNA modification for specialized translation in the two life stages of trypanosomes” and U.S. Binational Science Foundation (ref. 2015/219) from October 2015 to October 2019, entitled “The role and mechanism of RNA pseudo-uridylation and sugar methylation (Nm) during the developmental cycle of trypanosomes.” The work done in A.D.’s laboratory was supported by National Science Center SONATA BIS grant, entitled “Non-canonical RNA tailing and other post-transcriptional regulatory mechanisms in T cell-mediated adaptive immunity” (proposal ID: 492777, agreement no: UMO-2020/38/E/NZ2/00372, start date: 22 March 2021, end date: 21 March 2026); National Science Center OPUS grant, entitled “Analysis of the role of cytoplasmic polyadenylation in the regulation of the innate immune response” (proposal ID: 443521, agreement no.: UMO-2019/33/B/NZ2/01773, start date: 2 March 2020, end date: 1 March 2023); and European Union’s Horizon 2020 (H2020-WIDESPREAD-03-2017)–ERAChair, entitled “MOlecular Signaling in Health and Disease - Interdisciplinary Centre of Excellence” (acronym: MOSaIC, agreement no.: 810425, implementation period: start date: 1 November 2018, end date: 31 October 2023).American Association for the Advancement of ScienceRepositório da Universidade de LisboaGuegan, Fabien MarcRajan, K. ShanmughaBento, FabioNeves, DanielSequeira, MarianaGumińska, NataliaMroczek, SewerynDziembowski, AndrzejCohen-Chalamish, SmadarDoniger, TirzaGalili, BeathriceEstévez, Antonio M.Notredame, CedricMichaeli, ShulamitFigueiredo, Luisa M.2022-07-18T16:57:04Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53851engSci Adv. 2022 Jun 17;8(24):eabn270610.1126/sciadv.abn27062375-2548info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:21Zoai:repositorio.ul.pt:10451/53851Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:27.881157Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A long noncoding RNA promotes parasite differentiation in African trypanosomes
title A long noncoding RNA promotes parasite differentiation in African trypanosomes
spellingShingle A long noncoding RNA promotes parasite differentiation in African trypanosomes
Guegan, Fabien Marc
title_short A long noncoding RNA promotes parasite differentiation in African trypanosomes
title_full A long noncoding RNA promotes parasite differentiation in African trypanosomes
title_fullStr A long noncoding RNA promotes parasite differentiation in African trypanosomes
title_full_unstemmed A long noncoding RNA promotes parasite differentiation in African trypanosomes
title_sort A long noncoding RNA promotes parasite differentiation in African trypanosomes
author Guegan, Fabien Marc
author_facet Guegan, Fabien Marc
Rajan, K. Shanmugha
Bento, Fabio
Neves, Daniel
Sequeira, Mariana
Gumińska, Natalia
Mroczek, Seweryn
Dziembowski, Andrzej
Cohen-Chalamish, Smadar
Doniger, Tirza
Galili, Beathrice
Estévez, Antonio M.
Notredame, Cedric
Michaeli, Shulamit
Figueiredo, Luisa M.
author_role author
author2 Rajan, K. Shanmugha
Bento, Fabio
Neves, Daniel
Sequeira, Mariana
Gumińska, Natalia
Mroczek, Seweryn
Dziembowski, Andrzej
Cohen-Chalamish, Smadar
Doniger, Tirza
Galili, Beathrice
Estévez, Antonio M.
Notredame, Cedric
Michaeli, Shulamit
Figueiredo, Luisa M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Guegan, Fabien Marc
Rajan, K. Shanmugha
Bento, Fabio
Neves, Daniel
Sequeira, Mariana
Gumińska, Natalia
Mroczek, Seweryn
Dziembowski, Andrzej
Cohen-Chalamish, Smadar
Doniger, Tirza
Galili, Beathrice
Estévez, Antonio M.
Notredame, Cedric
Michaeli, Shulamit
Figueiredo, Luisa M.
description Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)
publishDate 2022
dc.date.none.fl_str_mv 2022-07-18T16:57:04Z
2022
2022-01-01T00:00:00Z
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.uri.fl_str_mv http://hdl.handle.net/10451/53851
url http://hdl.handle.net/10451/53851
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Sci Adv. 2022 Jun 17;8(24):eabn2706
10.1126/sciadv.abn2706
2375-2548
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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