| Full text | |
| Author(s): Show less - |
Shiburah, Mark E.
;
de Oliveira, Beatriz Cristina D.
;
Bisetegn, Habtye
;
de Oliveira, Leilane S.
;
Passos, Arthur O.
;
Silva, Debora A.
;
Assis, Luiz Henrique C.
;
Alves, Cristiane S.
;
Ernst, Evan
;
Mena-Barreto, Rubem
;
Batista, Marcos M.
;
Soeiro, Maria de Nazare C.
;
Menozzi, Benedito D.
;
Langoni, Helio
;
Aoki, Juliana I.
;
Coelho, Adriano C.
;
Miranda Junior, Adalberto S.
;
Machado, Carlos Renato
;
Cano, Maria Isabel N.
Total Authors: 19
|
| Document type: | Journal article |
| Source: | International Journal of Biological Macromolecules; v. 323, p. 21-pg., 2025-09-01. |
| 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 gamma H2A 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. (AU) | |
| FAPESP's process: | 24/20110-0 - EXPLORING THE FUNCTIONS OF LONG NON-CODING RNA TERRA IN THE REGULATION OF TELOMERE MAINTENANCE IN Leishmania major |
| Grantee: | Leilane Silva de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 16/21171-6 - Paromomycin for the treatment of Tegumentary Leishmaniasis: investigation in vitro, in vivo and in the identification of molecular markers associated with susceptibility and resistance |
| Grantee: | Adriano Cappellazzo Coelho |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 20/00316-1 - Studies about the function of L. major TERT component in telomere maintenance and cell proliferation |
| Grantee: | Mark Ewusi Shiburah |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 21/04253-7 - Role of TERRA in telomere regulation and replicative senescence in Leishmania major |
| Grantee: | Luiz Henrique de Castro Assis |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 24/00995-7 - Composition of the telomerase ribonucleoprotein complex of Leishmania major and Leishmania infantum with different genetic backgrounds |
| Grantee: | Beatriz Cristina Dias de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 21/05523-8 - Composition of the telomerase ribonucleoprotein complex of Leishmania major and Leishmania infantum with different genetic backgrounds |
| Grantee: | Débora Andrade Silva |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 18/04375-2 - Studies about the biogenesis and composition of the Leishmania spp. ribonucleoprotein complex and its regulation |
| Grantee: | Maria Isabel Nogueira Cano |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 24/23269-0 - Comparative genomic and transcriptomic studies of Leishmania major depleted of basic components of telomerase |
| Grantee: | Arthur de Oliveira Passos |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 23/16161-5 - Characterization of the telomerase reverse transcriptase (TERT) component of Leishmania infantum and assessment of its role in telomere maintenance, genome integrity, cell cycle progression, and parasite infectivity |
| Grantee: | Habtye Bisetegn Endalamaw |
| Support Opportunities: | Scholarships in Brazil - Doctorate |