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Role of TERRA in telomere regulation and replicative senescence in Leishmania major

Grant number: 21/04253-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2021
Effective date (End): May 31, 2023
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal researcher:Maria Isabel Nogueira Cano
Grantee:Luiz Henrique de Castro Assis
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:18/04375-2 - Studies about the biogenesis and composition of the Leishmania spp. ribonucleoprotein complex and its regulation, AP.TEM

Abstract

Among the protozoa of the Leishmania genus are the causative agents of leishmaniasis, a neglected tropical disease that presents different clinical forms and that affects millions of people in Brazil and in the world. To date there are no efficient control and treatment against leishmaniasis, therefore, studies that contribute to understanding parasite biology may provide the possibility to find new therapeutic targets. Among these new potential targets are telomeres. Telomeres are nucleoprotein structures that protect the chromosomal ends from fusion and degradation and their main function is to maintain genome stability, which if disturbed, can directly affect both cell life span and survival. Some time ago, it was shown that telomeres from different eukaryotes are transcribed into long non-coding RNAs called TERRA (telomeric repeat-containing RNA). TERRA transcripts are involved with telomere length maintenance in different ways. Our research group has recently identified and characterized TERRA transcripts expressed from different Leishmania major life stages during the parasite developmental cycle. In Leishmania, TERRA transcripts have variable sizes, and their expression profile depends on the parasite developmental stage. Interestingly, parasites with an increased population doubling present an increase in the abundance of TERRA transcripts and telomeres shortening, suggesting that they reach their proliferative capacity and enter replicative senescence. A similar phenomenon has been described in other eukaryotes. Thus, the objective of this work is to characterize the role of TERRA in L. major telomere biology and to improve our knowledge about the importance of telomeres for parasite survival. (AU)