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Impact on the Leishmania mexicana transcriptome due to knockout of genes encoding orthologs of methyltransferases involved in m1A and m5C mRNA modifications

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Autor(es):
Bezerra, Angela Moreira ; Leite, Ariely Barbosa ; Reis, Christian Robson de Souza ; Pitta, Joao Luiz de Lemos Padilha ; Maran, Suellen Rodrigues ; Moretti, Nilmar Silvio ; Moura, Danielle Maria Nascimento ; Rezende, Antonio Mauro
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: PARASITES & VECTORS; v. 18, n. 1, p. 18-pg., 2025-07-31.
Resumo

BackgroundChemical modifications of mRNAs constitute an alternative mechanism for gene expression regulation, which involves proteins responsible for adding, recognizing and removing these modifications. While orthologs of enzymes involved in adding m1A (TRMT6/TRMT61A) and m5C (NSUN2) modifications are present in trypanosomatid species, a clear understanding of their biological role in these parasites is necessary.MethodsTo shed light on this, we genetically manipulated the TRMT61A and NSUN2 protein-encoding genes in the Leishmania mexicana species using the CRISPR-Cas9 editing technique and analyzed the impact on cell growth and differentiation as well as the global gene expression profile.ResultsDeletion of the genes investigated here caused changes in the normal pattern of L. mexicana differentiation, and functional analyses of differentially expressed genes in the mutants unveiled significant biological effects. For the TRMT61A gene, transcripts related to nucleotide metabolism, translation, protein folding and refolding were affected. For the NSUN2 genes, enrichment analysis indicated impacts on biological processes mostly related to nucleotide metabolism and DNA binding.ConclusionsOur findings provide insights into the role of these methyltransferases orthologs in the regulation of trypanosomatid transcriptome, contributing to our understanding of gene expression control in this parasite. (AU)

Processo FAPESP: 23/16672-0 - Papel da modificação de RNA ac4C na diferenciação das formas evolutivas de Leishmania
Beneficiário:Ariely Barbosa Leite
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 22/03075-0 - Desvendando os mecanismos regulatórios envolvidos na relação parasito hospedeiro da Leishmania: foco nas alterações pós-transcricionais e pós-traducionais
Beneficiário:Nilmar Silvio Moretti
Modalidade de apoio: Auxílio à Pesquisa - Projeto Inicial
Processo FAPESP: 18/09948-0 - Estudo da acetilação proteica em Leishmania
Beneficiário:Nilmar Silvio Moretti
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 21/13477-6 - DeaceLeish: investigando o papel das lisinas desacetilases nos mecanismos de regulação da diferenciação dos estágios evolutivos de Leishmania mexicana
Beneficiário:Suellen Rodrigues Maran
Modalidade de apoio: Bolsas no Brasil - Doutorado