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

• Grant number: 19/11496-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2019
• End date: July 27, 2020
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Maria Isabel Nogueira Cano
• Grantee: Edna Gicela Ortiz Morea
• Host 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 contol and treatment against leishmaniasis, therefore, studies that contribute to understand 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 size, and its expression profile depends on the parasite developmental stage. Interestingly, parasite with 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. 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.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ARAUJO, SARA A.; MARTINS, GUSTAVO H.; QUEL, NATALIA G.; ARAGAO, ANNELIZE Z. B.; MOREA, EDNA G. O.; BORGES, JULIO C.; HOURY, WALID A.; CANO, MARIA I. N.; RAMOS, I, CARLOS H.. Purification and characterization of a novel and conserved TPR-domain protein that binds both Hsp90 and Hsp70 and is expressed in all developmental stages of Leishmania major. Biochimie, v. 182, p. 51-60, MAR 2021. (14/25967-4, 12/50161-8, 19/11496-3, 18/04375-2, 17/26131-5)

ABRAHAO, JOSIELLE; AMARO, BARBARA T.; PERES, BARBARA R.; QUEL, NATALIA G.; ARAGA, ANNELIZE Z. B.; MOREA, EDNA G. O.; CANO, MARIA ISABEL N.; HOURY, WALID A.; RAMOS, CARLOS H. I.. Leishmania major RUVBL1 has a hexameric conformation in solution and, in the presence of RUVBL2, forms a heterodimer with ATPase activity. Archives of Biochemistry and Biophysics, v. 703, MAY 30 2021. (15/13521-4, 13/10939-2, 14/25967-4, 12/50161-8, 19/11496-3)

ORTIZ MOREA, EDNA GICELA; VASCONCELOS, ELTON JOSE ROSAS; ALVES, CRISTIANE DE SANTIS; GIORGIO, SELMA; MYLER, PETER J.; LANGONI, HELIO; AZZALIN, CLAUS MARIA; NOGUEIRA CANO, MARIA ISABEL. Exploring TERRA during Leishmania major developmental cycle and continuous in vitro passages. International Journal of Biological Macromolecules, v. 174, p. 573-586, MAR 31 2021. (19/11496-3, 18/04375-2, 18/23302-6)

FERNANDES, CARLOS A. H.; MOREA, EDNA GICELA O.; DOS SANTOS, GABRIEL A.; DA SILVA, VITOR L.; VIEIRA, MARINA ROVERI; VIVIESCAS, MARIA ALEJANDRA; CHATAIN, JEAN; VADEL, AURELIE; SAINTOME, CAROLE; FONTES, MARCOS ROBERTO M.; et al. A multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensis. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1864, n. 7, JUL 2020. (15/17286-0, 18/04375-2, 19/11496-3)