Shiburah, Mark E, de Oliveira, Beatriz Cristina D, Bisetegn, Habtye, de Oliveira, Leilane S, Passos, Arthur O, Silva, Débora A, Assis, Luiz Henrique C, Alves, Cristiane S, Ernst, Evan, Barreto, Rubem M, Batista, Marcos M, Soeiro, Maria de Nazaré C, Menozzi, Benedito D, Langoni, Helio, Aoki, Juliana I, Coelho, Adriano C, Miranda Junior, Adalberto S, Machado, Carlos Renato, Cano, Maria Isabel N (August 2025) The absence of the Leishmania major telomerase TERT component links telomeres and cell homeostasis with infectivity. International Journal of Biological Macromolecules. p. 147036. ISSN 0141-8130
Abstract
We studied the impacts of deleting the telomerase reverse transcriptase component of the Leishmania major (LmTERT) telomerase complex. The Leishmania genus comprises species that cause leishmaniasis, a neglected disease that lacks effective treatment and control options, highlighting the need for alternative therapeutics. Telomerase plays a crucial role in maintaining the integrity of eukaryotic genomes by synthesizing telomeres through its TERT and telomerase RNA components. Here, we show that the absence of TERT in L. major has a pleiotropic effect on parasite homeostasis, causing growth and proliferation alterations, progressive telomere shortening, increased TERRA expression, and γH2A signaling, besides the early onset of autophagosomes and mitochondrial insults. The proteomic analysis of LmTERT knockout promastigotes compared with the parental lineage confirmed some of these alterations, showing an imbalance in constituents of chromatin, plasma membrane, mitochondria, and cytoskeleton, and the unexpected presence of proteins involved in autophagy and virulence at this parasite life stage. Inactivating LmTERT also impaired metacyclogenesis, abolishing the parasite's infectivity. These results establish a strong link between telomeres, cell homeostasis, and the parasite's infective capability, highlighting LmTERT as a promising target for antiparasitic strategies.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > telomerase |
| CSHL Authors: | |
| Communities: | CSHL labs > Martienssen lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 21 August 2025 |
| Date Deposited: | 25 Aug 2025 12:33 |
| Last Modified: | 25 Aug 2025 12:33 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41946 |
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