Characterization of the mechanisms of action of long non-coding RNAs involved with gene activation programs in human cells

• Grant number: 14/03620-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2014
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Sergio Verjovski Almeida
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: João Carlos Setubal ; Mari Cleide Sogayar
• Associated scholarship(s): 15/00324-6 - Study of the control of gene expression lncRNA INXS involved in the apoptosis, BP.DR; 14/25481-4 - Liposomes as vehicles of delivery of the lncRNA INXS to tumor cells in vitro and in vivo to induction of apoptosis, BP.IC

Abstract

In the past years, with the large scale sequencing data from the public ENCODE project, it became evident that up to 92% of the human genome can be transcribed, and that the tens of thousands long (> 200 nucleotides) non-coding RNAs (lncRNAs) that have been catalogued so far represent the most diverse and most abundant class of RNAs in a cell, excepting the ribosomal RNAs. In spite of that, only about two-dozen lncRNAs have their molecular mechanisms of action elucidated and characterized in detail, revealing their role as regulators of gene transcription in mammals. The present challenge is to find the most relevant experimental models and cellular processes, searching for key lncRNAs in these processes, and to show the loss or gain of function, in a given cell type, when one of these lncRNAs is deleted or over-expressed. The proposed project focuses on three relevant cellular processes - response to androgen hormone, apoptosis, and differentiation of human embryonic stem cells into neural crest cells - and has the advantage of having already obtained preliminary results about three novel lncRNAs that are strong candidates of having regulatory roles over some of the steps in each of these three biological processes. These three lncRNAs are, respectively, lincPSA, INXS and TFAP2A-AS2. Applying new technologies to detect the interactions between lncRNAs, proteins and their possible binding sites on genomic DNA, and the detection in parallel of changes in histone marks and in transcriptional activities of genes, as proposed here, will permit understanding the role of each of these three lncRNAs, and knowledge of these mechanisms may open the door to an eventual use of these lncRNAs as therapeutical targets. (AU)

Scientific publications

(10)

(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)

SHERIDAN, MEGAN A.; YUNUSOV, DINAR; BALARAMAN, VELMURUGAN; ALEXENKO, ANDREI P.; YABE, SHINICHIRO; VERJOVSKI-ALMEIDA, SERGIO; SCHUST, DANNY J.; FRANZ, ALEXANDER W.; SADOVSKY, YOEL; TOSHIHIKO, EZASHI; et al. Vulnerability of primitive human placental trophoblast to Zika virus. Proceedings of the National Academy of Sciences of the United States of America, v. 114, n. 9, p. E1587-E1596, FEB 28 2017. (10/51152-7, 14/03620-2)

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)

DASILVA, LUCAS F.; BECKEDORFF, FELIPE C.; AYUPE, ANA C.; AMARAL, MURILO S.; MESEL, VINICIUS; VIDEIRA, ALEXANDRE; REIS, EDUARDO M.; SETUBAL, JOAO C.; VERJOVSKI-ALMEIDA, SERGIO. Chromatin Landscape Distinguishes the Genomic Loci of Hundreds of Androgen-Receptor-Associated LincRNAs From the Loci of Non-associated LincRNAs. FRONTIERS IN GENETICS, v. 9, APR 25 2018. (14/03620-2)

DE CAIRES, JR., LUIZ CARLOS; GOULART, ERNESTO; MELO, UIRASOUTO; HENRIQUE ARAUJO, BRUNO SILVA; ALVIZI, LUCAS; SCHANOSKI, ALESSANDRA SOARES; DE OLIVEIRA, DANYLLO FELIPE; KOBAYASHI, GERSON SHIGERU; GRIESI-OLIVEIRA, KARINA; MUSSO, CAMILA MANSO; et al. Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. NATURE COMMUNICATIONS, v. 9, FEB 2 2018. (14/50931-3, 14/03620-2, 13/08028-1)

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)

YUNUSOV, DINAR; ANDERSON, LETICIA; DASILVA, LUCAS FERREIRA; WYSOCKA, JOANNA; EZASHI, TOSHIHIKO; ROBERTS, R. MICHAEL; VERJOVSKI-ALMEIDA, SERGIO. HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines. SCIENTIFIC REPORTS, v. 6, SEP 8 2016. (14/03620-2)

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)

SHERIDAN, MEGAN A.; YUNUSOV, DINAR; BALARAMAN, VELMURUGAN; ALEXENKO, ANDREI P.; YABE, SHINICHIRO; VERJOVSKI-ALMEIDA, SERGIO; SCHUST, DANNY J.; FRANZ, ALEXANDER W.; SADOVSKY, YOEL; TOSHIHIKO, EZASHI; et al. Vulnerability of primitive human placental trophoblast to Zika virus. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 114, n. 9, p. 10-pg., 2017-02-28. (14/03620-2, 10/51152-7)

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)

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, p. 16-pg., 2021-01-11. (12/12005-4, 18/23693-5, 15/00324-6, 14/03620-2)