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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 type:Research Projects - Thematic Grants
Duration: July 01, 2014 - June 30, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Sergio Verjovski Almeida
Grantee:Sergio Verjovski Almeida
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo, SP, Brazil
Assoc. 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)

Articles published in Agência FAPESP about the research grant
RNA molecules appear to regulate action of male hormone in prostate cancer 

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)
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. Web of Science Citations: 0.
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; AMARAL, MURILOSENA; DASILVA, LUCAS FERREIRA; ASTRAY, RENATO MANCINI; SUAREZ-PATINO, SANDRA FERNANDA; VENTINI, DANIELLA CRISTINA; DA SILVA, SERGIO GOMES; YAMAMOTO, GUILHERME LOPES; EZQUINA, SUZANA; NASLAVSKY, MICHEL SATYA; ALVES SILVA, KAYQUE TELLES; WEINMANN, KARINA; VAN DER LINDEN, VANESSA; VAN DER LINDEN, HELIO; RICARDO DE OLIVEIRA, JOAO MENDES; MARIA ARRAIS, NIVIA RODRIGUES; MELO, ADRIANA; FIGUEIREDO, THALITA; SANTOS, SILVANA; GOES MEIRA, JOANNA CASTRO; PASSOS, SAULO DUARTE; DE ALMEIDA, ROQUE PACHECO; BISPO, ANA JOVINABARRETO; CAVALHEIRO, ESPERABRAO; KALIL, JORGE; CUNHA-NETO, EDECIO; NAKAYA, HELDER; SANTOS, ROBERT ANDREATA; DE SOUZA FERREIRA, LUIS CARLOS; VERJOVSKI-ALMEIDA, SERGIO; HO, PAULO LEE; PASSOS-BUENO, MARIA RITA; ZATZ, MAYANA. Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. NATURE COMMUNICATIONS, v. 9, FEB 2 2018. Web of Science Citations: 6.
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; ROBERTS, R. MICHAEL. 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. Web of Science Citations: 37.
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. Web of Science Citations: 5.

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