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Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes


In recent years, with the intensive use of large-scale sequencing replacing microarrays for the detection of gene expression in several organisms, it has become clear that, in all eukaryotes studied so far, thousands of long (> 200 nucleotides) non-protein coding RNAs (lncRNAs) represent a very diverse and very tissue-specific class of RNAs in a cell. Despite this, only about four dozen lncRNAs in humans have had their molecular mechanisms of action identified and characterized in detail, which has revealed their role as regulators of gene transcription in eukaryotes. The current challenge is still to find the most relevant experimental models and cellular processes, looking for lncRNAs that are key targets in these processes, and to show the loss and gain of function in a particular cell type or organ when the transcription of one of these lncRNAs is repressed or it is over-expressed. The project proposed here focuses on relevant cellular processes in two species, the human and the parasite Schistosoma mansoni, which have been the study interest of our group in the last 15 years. In humans, we will study the involvement of lncRNAs in human embryonic stem cell differentiation programs into neural cortex cells and into placental trophoblasts, and the involvement of lncRNAs in androgen regulation of prostate cancer. In S. mansoni we will study the role of lncRNAs in the sexual maturation of parasites, the role of lncRNAs in the response of parasites to drugs, and the involvement of lncRNAs during in vitro parasite death induced by immunized sera of infected Rhesus monkeys that had self-cured from the disease. The project has the advantage of having already obtained preliminary results on new lncRNAs that are candidates to have regulatory roles on some of these biological processes. The application of new technologies to detect the interaction between lncRNAs, proteins and their possible binding sites in genomic DNA, and the parallel detection of the modifications of chromatin marks and the transcriptional activity of genes proposed here, will allow us to understand the regulatory role of lncRNAs, and knowledge of these mechanisms may open doors to the eventual use of these lncRNAs as therapeutic targets. (AU)

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Scientific publications (9)
(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)
AMARAL, MURILO SENA; GOULART, ERNESTO; CAIRES-JUNIOR, LUIZ CARLOS; MORALES-VICENTE, DAVID ABRAHAM; SOARES-SCHANOSKI, ALESSANDRA; GOMES, ROSELANE PAIVA; OLBERG, GIOVANNA GONCALVES DE OLIVEIRA; ASTRAY, RENATO MANCINI; KALIL, JORGE E.; ZATZ, MAYANA; et al. Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins. PLoS Neglected Tropical Diseases, v. 14, n. 8, . (14/03620-2, 13/08028-1, 14/50931-3, 18/23693-5)
SILVEIRA, GILBERT O.; COELHO, HELENA S.; AMARAL, MURILO S.; VERJOVSKI-ALMEIDA, SERGIO. Long non-coding RNAs as possible therapeutic targets in protozoa, and in Schistosoma and other helminths. Parasitology Research, . (18/23693-5, 18/24015-0)
TAHIRA, ANA C.; VERJOVSKI-ALMEIDA, SERGIO; FERREIRA, SERGIO T.. Dementia is an age-independent risk factor for severity and death in COVID-19 inpatients. ALZHEIMERS & DEMENTIA, v. 17, n. 11, p. 1818-1831, . (18/23693-5)
AMARAL, MURILO S.; MACIEL, LUCAS F.; SILVEIRA, GILBERT O.; OLBERG, GIOVANNA G. O.; LEITE, JOAO V. P.; IMAMURA, LUCAS K.; PEREIRA, ADRIANA S. A.; MIYASATO, PATRICIA A.; NAKANO, ELIANA; VERJOVSKI-ALMEIDA, SERGIO. Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni. SCIENTIFIC REPORTS, v. 10, n. 1, . (18/19591-2, 18/23693-5, 16/10046-6, 18/24015-0)
TAHIRA, ANA C.; VERJOVSKI-ALMEIDA, SERGIO; FERREIRA, SERGIO T.. Dementia is an age-independent risk factor for severity and death in COVID-19 inpatients. ALZHEIMERS & DEMENTIA, . (18/23693-5)
MACIEL, LUCAS F.; MORALES-VICENTE, DAVID A.; VERJOVSKI-ALMEIDA, SERGIO. Dynamic Expression of Long Non-Coding RNAs Throughout Parasite Sexual and Neural Maturation in Schistosoma Japonicum. NON-CODING RNA, v. 6, n. 2, . (14/03620-2, 18/19591-2, 18/23693-5)
VIDEIRA, ALEXANDRE; BECKEDORFF, FELIPE C.; DASILVA, LUCAS F.; VERJOVSKI-ALMEIDA, SERGIO. PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors. CELL COMMUNICATION AND SIGNALING, v. 19, n. 1, . (15/00324-6, 18/23693-5, 12/12005-4, 14/03620-2)
MACIEL, LUCAS F.; MORALES-VICENTE, DAVID A.; SILVEIRA, GILBERT O.; RIBEIRO, RAPHAEL O.; OLBERG, GIOVANNA G. O.; PIRES, DAVID S.; AMARAL, MURILO S.; VERJOVSKI-ALMEIDA, SERGIO. Weighted Gene Co-Expression Analyses Point to Long Non-Coding RNA Hub Genes at Different Schistosoma mansoni Life-Cycle Stages. FRONTIERS IN GENETICS, v. 10, . (14/03620-2, 17/22379-2, 18/24015-0, 18/23693-5)
AMARAL, MURILO SENA; SANTOS, DAISY WOELLNER; PEREIRA, ADRIANA S. A.; TAHIRA, ANA CAROLINA; MALVEZZI, JOAO V. M.; MIYASATO, PATRICIA AOKI; FREITAS, RAFAELA DE PAULA; KALIL, JORGE; FAT, ELISA M. TJON KON; DE DOOD, CLAUDIA J.; et al. Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge. NATURE COMMUNICATIONS, v. 12, n. 1, . (16/10046-6, 15/06366-2, 19/09404-3, 18/15049-9, 18/18117-5, 18/23693-5)

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