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

• Grant number: 18/23693-5
• Support Opportunities: Research Projects - Thematic Grants
• Duration: July 01, 2019 - June 30, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Sergio Verjovski Almeida
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Chao Yun Irene Yan ; Christoph Grunau ; Eliana Nakano ; Felipe Cesar Ferrarezi Beckedorff ; João Carlos Setubal ; Jorge Elias Kalil Filho ; Mayana Zatz ; Murilo Sena Amaral ; Ronaldo de Carvalho Augusto
• Associated grant(s): 22/05770-8 - ICOPA 2022 15th International congress of Parasitology, AR.EXT
• Associated scholarship(s): 21/13698-2 - Functional characterization of the PVT1 lincRNA associated with androgen receptor in prostate Cancer, BP.IC; 21/06005-0 - Identification of long non-coding RNAs involved in the cell development regulation program of human trophoblasts, BP.DR; 20/02976-9 - Characterization of the interaction sites in the genome of the PVT1 lincRNA associated with the androgen receptor in Prostate Cancer lineages, BP.PD

Abstract

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)

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, AUG 2020. (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, DEC 2021. (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, NOV 2021. (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, DEC 9 2020. (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, APR 2021. (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, JUN 2020. (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, JAN 11 2021. (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, SEP 12 2019. (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, OCT 26 2021. (16/10046-6, 15/06366-2, 19/09404-3, 18/15049-9, 18/18117-5, 18/23693-5)