Leishmania major telomerase RNA knockout: From altered cell proliferation to decreased parasite infectivity

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorCouncil for Scientific and Industrial Research (CSIR-ARI)-
Autor(es): dc.contributorWollo University-
Autor(es): dc.contributorHoward Hughes Medical Institute/Cold Spring Harbor Laboratory-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorOswaldo Cruz Foundation-
Autor(es): dc.creatorde Oliveira, Beatriz Cristina Dias-
Autor(es): dc.creatorShiburah, Mark Ewusi-
Autor(es): dc.creatorAssis, Luiz Henrique Castro-
Autor(es): dc.creatorFontes, Veronica Silva-
Autor(es): dc.creatorBisetegn, Habtye-
Autor(es): dc.creatorPassos, Arthur de Oliveira-
Autor(es): dc.creatorde Oliveira, Leilane S.-
Autor(es): dc.creatorAlves, Cristiane de Santis-
Autor(es): dc.creatorErnst, Evan-
Autor(es): dc.creatorMartienssen, Rob-
Autor(es): dc.creatorGallo-Francisco, Pedro Henrique-
Autor(es): dc.creatorGiorgio, Selma-
Autor(es): dc.creatorBatista, Marcos Meuser-
Autor(es): dc.creatorSoeiro, Maria de Nazaré Correia-
Autor(es): dc.creatorMenna-Barreto, Rubem Figueiredo Sadok-
Autor(es): dc.creatorAoki, Juliana Ide-
Autor(es): dc.creatorCoelho, Adriano Cappellazzo-
Autor(es): dc.creatorCano, Maria Isabel Nogueira-
Data de aceite: dc.date.accessioned2025-08-21T19:37:42Z-
Data de disponibilização: dc.date.available2025-08-21T19:37:42Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.ijbiomac.2024.135150-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/308665-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/308665-
Descrição: dc.descriptionThis study focuses on the biological impacts of deleting the telomerase RNA from Leishmania major (LeishTER), a parasite responsible for causing leishmaniases, for which no effective treatment or prevention is available. TER is a critical player in the telomerase ribonucleoprotein complex, containing the template sequence copied by the reverse transcriptase component during telomere elongation. The success of knocking out both LeishTER alleles was confirmed, and no off-targets were detected. LmTER−/− cells share similar characteristics with other TER-depleted eukaryotes, such as altered growth patterns and partial G0/G1 cell cycle arrest in early passages, telomere shortening, and elevated TERRA expression. They also exhibit increased γH2A phosphorylation, suggesting that the loss of LeishTER induces DNA damage signaling. Moreover, pro-survival autophagic signals and mitochondrion alterations were shown without any detectable plasma membrane modifications. LmTER−/− retained the ability to transform into metacyclics, but their infectivity capacity was compromised. Furthermore, the overexpression of LeishTER was also deleterious, inducing a dominant negative effect that led to telomere shortening and growth impairments. These findings highlight TER's vital role in parasite homeostasis, opening discussions about its potential as a drug target candidate against Leishmania.-
Descrição: dc.descriptionASCRS Research Foundation-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Biosciences Institute São Paulo State University (UNESP), Sao Paulo-
Descrição: dc.descriptionAnimal Research Institute Council for Scientific and Industrial Research (CSIR-ARI)-
Descrição: dc.descriptionDepartment of Medical Laboratory Sciences College of Medicine and Health Sciences Wollo University-
Descrição: dc.descriptionHoward Hughes Medical Institute/Cold Spring Harbor Laboratory-
Descrição: dc.descriptionDepartment of Animal Biology Biology Institute University of Campinas (UNICAMP), Sao Paulo-
Descrição: dc.descriptionCellular Biology Laboratory Oswaldo Cruz Institute Oswaldo Cruz Foundation, Rio de Janeiro-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Biosciences Institute São Paulo State University (UNESP), Sao Paulo-
Descrição: dc.descriptionCNPq: 163895/2022-8-
Descrição: dc.descriptionFAPESP: 2016/21171-6-
Descrição: dc.descriptionFAPESP: 2018/04375-2-
Descrição: dc.descriptionFAPESP: 2019/11061-7-
Descrição: dc.descriptionFAPESP: 2019/25985-6-
Descrição: dc.descriptionFAPESP: 2020/00316-1-
Descrição: dc.descriptionFAPESP: 2021/04253-7-
Descrição: dc.descriptionCNPq: 302433/2019-8-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Biological Macromolecules-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectAltered cell proliferation-
Palavras-chave: dc.subjectDecreased infectivity capacity-
Palavras-chave: dc.subjectLeishmania spp.-
Palavras-chave: dc.subjectTelomerase RNA knockout and overexpression-
Palavras-chave: dc.subjectTelomere shortening-
Palavras-chave: dc.subjectTERRA upregulation-
Título: dc.titleLeishmania major telomerase RNA knockout: From altered cell proliferation to decreased parasite infectivity-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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