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Studying the control of gene expression in Leishmania: post-translational modification, non coding RNAs, cis-elements and gene amplification

Abstract

Leishmania is an ancestral eukaryote and a human parasite of medical relevance. As a model organism it exhibits several odd biological process, mainly in what it concerns to RNA. This proposal's objectives are to decipher molecular f mechanisms to stand different modes of post-transcriptional regulation of gene expression in Leishmania. We aim to study conserved sequences present at the 3'UTRs of parasite's mRNAs. Another target of our study are the non coding RNAs (ncRNAs) which control gene expression throughout Leishmania life cycle and may be critical for the parasite adaptation to each host. We will investigate post-translational processes and gene amplification focused on their role on the control of gene expression in Leishmania. Our objectives are: (1) To study mechanisms of action of conserved 3'UTR sequences to control RNA "turnover" and/or translation in both stages of development in Leishmania, and to understand whether they are involved in the control of "transcriptional regulons' in the parasite; (2) To study ncRNAs function in Leishmania using highthrouput sequencing data (RNA-seq) and to select from the non-coding RNA sequence data generated a few ncRNAs differentially expressed in promastigotes/amastigotes to investigate their potential role in the regulation of gene expression and pathogenesis; (3) to study the biogenesis of ODD3, a putative non coding RNA, its mechanism of action and mRNA targets; (4) to investigate some epigenetic factors involved in the control of gene expression in leishmania such as protein methylation an degradation pathways and (5) characterization of gene amplification control played by the enzymes LmHus1 and LmRad9, which are part of the machinery involved in signaling of DNA damage. (AU)

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Scientific publications (7)
(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)
TERRAO, MONICA CRISTINA; ROSAS DE VASCONCELOS, ELTON JOSE; DEFINA, TANIA AQUINO; MYLER, PETER J.; CRUZ, ANGELA KAYSEL. Disclosing 3 ` UTR cis-elements and putative partners involved in gene expression regulation in Leishmania spp.. PLoS One, v. 12, n. 8, . (08/04969-8, 13/50219-9)
CARNEIRO ALVES-FERREIRA, ELIZA VANESSA; FERREIRA, TIAGO RODRIGUES; WALRAD, PEGINE; KAYE, PAUL M.; CRUZ, ANGELA KAYSEL. Leishmania braziliensis prostaglandin F-2 alpha synthase impacts host infection. PARASITES & VECTORS, v. 13, n. 1, . (13/50219-9, 11/02040-4, 14/19400-1, 10/20597-3)
CASTRO, FELIPE FREITAS; RUY, PATRICIA C.; ZEVIANI, KARMA NOGUEIRA; SANTOS, RAMON FREITAS; TOLEDO, JULIANO SIMOES; CRUZ, ANGELA KAYSEL. Evidence of putative non-coding RNAs from Leishmania untranslated regions. Molecular and Biochemical Parasitology, v. 214, p. 69-74, . (12/16749-8, 09/14184-0, 13/50219-9, 12/17025-3)
RUY, PATRICIA DE CASSIA; MONTEIRO-TELES, NATALIA MELQUIE; MISERANI MAGALHAES, RUBENS DANIEL; FREITAS-CASTRO, FELIPE; DIAS, LEANDRO; AQUINO DEFINA, TANIA PAULA; DE VASCONCELOS, ELTON JOSE ROSAS; MYLER, PETER J.; CRUZ, ANGELA KAYSEL. Comparative transcriptomics in Leishmania braziliensis: disclosing differential gene expression of coding and putative noncoding RNAs across developmental stages. RNA BIOLOGY, v. 16, n. 5, p. 639-660, . (15/16684-1, 13/50219-9)
CRUZ, ANGELA KAYSEL; FREITAS-CASTRO, FELIPE. Genome and transcriptome analyses of Leishmania spp.: opening Pandora's box. Current Opinion in Microbiology, v. 52, p. 64-69, . (13/50219-9)
GARCIA, JULIANA B. F.; VIEIRA DA ROCHA, JOAO P.; COSTA-SILVA, HELLIDA M.; ALVES, CERES L.; MACHADO, CARLOS R.; CRUZ, ANGELA K.. Leishmania major and Trypanosoma cruzi present distinct DNA damage responses. Molecular and Biochemical Parasitology, v. 207, n. 1, p. 23-32, . (10/20597-3, 13/50219-9)
SHARMA, ROHIT; TERRAO, MONICA CRISTINA; CASTRO, FELIPE FREITAS; BREITLING, REINHARD; FACA, VITOR; OLIVEIRA, EDUARDO BRANDT; CRUZ, ANGELA KAYSEL. Insights on a putative aminoacyl-tRNA-protein transferase of Leishmania major. PLoS One, v. 13, n. 9, . (13/50219-9, 11/24086-6)

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