| Grant number: | 14/50308-4 |
| Support type: | Regular Research Grants |
| Duration: | August 01, 2014 - July 31, 2016 |
| Field of knowledge: | Interdisciplinary Subjects |
| Cooperation agreement: | University of Cambridge |
| Principal Investigator: | Helder Takashi Imoto Nakaya |
| Grantee: | Helder Takashi Imoto Nakaya |
| Principal investigator abroad: | Tony Kouzarides |
| Institution abroad: | University of Cambridge, England |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 12/19278-6 - Systems biology of long non-coding RNAs, AP.JP |
Abstract
It is estimated that thousands of long non-coding RNAs (IncRNAs) are transcribed in the genome of several organisms. Dr. Kouzarides' group at Cambridge University re-analyzed a vast amount of RNA-sequencing data, and identified -600 IncRNAs that were "positionally conserved" (pcRNAs) in human and mo use genomes. Among the genes associated with these pcRNAs, a striking enrichment was observed for loci related to embryonic and tissue development. They also demonstrated that pcRNA expression is highly tissue-specific and directly correlates with the associated coding genes, supporting the idea that pcRNAs are context-specific regulators of developmental genes. Our group at University of São Paulo is utilizing publicly available high-throughput data to investigate the expression of IncRNAs under hundreds of different perturbations and conditions, and studying the implication of IncRNAs in the regulation of candidate target genes. We compared the genomic regions of these -600 pcRNAs with the genomic regions of probes from different microarray platforms and found that most of these pcRNAs are represented by one or more probes. Here we propose to analyse the expression patterns of these pcRNAs, and how their expression correlates with the expression of coding genes, in a large panel of human cancer cell lines, primary tumours and disease conditions. The functions of a number of selected pcRNAs will be validated by Dr. Kouzarides' group. By assessing the transcription of pcRNAs and their associated coding genes in thousands of microarray studies, we expect to identify the biological conditions that affect the most the expression of pcRNAs and to reveal interesting mechanisms of gene regulation. (AU)