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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Parasite and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1513908

A short ncRNA modulates gene expression and affects stress response and parasite differentiation in Leishmania braziliensis

Provisionally accepted
José C Quilles José C Quilles 1Caroline Ricce Espada Caroline Ricce Espada 2Lissur A Orsine Lissur A Orsine 2Tânia P. Defina Tânia P. Defina 2Letícia Almeida Letícia Almeida 2Fabíola Holetz Fabíola Holetz 3Angela Kaysel Cruz Angela Kaysel Cruz 2*
  • 1 University of São Paulo, São Paulo, Brazil
  • 2 RIbeirão Preto Medical School, Department of Cell and Molecular Biology, University of São Paulo, São Paulo, Brazil
  • 3 Gene Expression Regulation Laboratory, Carlos Chagas Institute (ICC), Oswaldo Cruz Foundation, Curitiba, Paraná, Brazil

The final, formatted version of the article will be published soon.

    The protozoan parasite Leishmania spp. is a causative agent of leishmaniasis, a disease that affects millions of people in more than 80 countries worldwide. Apart from its medical relevance, this organism has a genetic organization that is unique among eukaryotes. Studies of the mechanisms regulating gene expression in Leishmania led us to investigate noncoding RNAs (ncRNAs) as regulatory elements. We previously identified differentially expressed (DE) ncRNAs in Leishmania braziliensis with potential roles in the parasite biology and development. Herein, we present a functional analysis of one such DE ncRNA, the 147-nucleotide-long transcript ncRNA97, which is preferentially expressed in amastigotes, the replicative form within mammalian phagocytes. By RT-qPCR the ncRNA97 was detected in greater quantities in the nucleus under physiological conditions and in the cytoplasm under nutritional stress. Interestingly, the transcript is protected at the 5' end but is not processed by the canonical trypanosomatid trans-splicing mechanism, according to the RNA circularization assay. ncRNA97 knockout ( KO ) and addback ( AB ) transfectants were generated and subjected to phenotypic analysis, which revealed that the lack of ncRNA97 impairs the starvation response and differentiation to the infective form. Comparative transcriptomics of ncRNA97 KO and parental cells revealed that transcripts encoding amastigote-specific proteins were affected. This pioneering work demonstrates that ncRNAs contribute to the developmental regulatory mechanisms of Leishmania.

    Keywords: noncoding RNA, Leishmania, Gene Expression, Metacyclogenesis, Nutritional stress

    Received: 19 Oct 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Quilles, Ricce Espada, Orsine, Defina, Almeida, Holetz and Kaysel Cruz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Angela Kaysel Cruz, RIbeirão Preto Medical School, Department of Cell and Molecular Biology, University of São Paulo, São Paulo, Brazil

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