Intragenic retrocopies and its host genes, an expression inter relationship to be uncovered in tumors

• Grant number: 20/08992-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2020
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Pedro Alexandre Favoretto Galante
• Grantee: David Berl
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated research grant: 18/15579-8 - Retroelements: a driving force generating genetic novelties in the human and mouse genome, AP.JP2

Abstract

Despite almost three decades of large-scale studies of the human transcriptome, we are still far from unraveling and understanding all of its complexities under normal conditions, especially in pathologies such as cancer. In this project we will study the expression of a specific group of elements, retrocopies (processed pseudogenes co located with coding genes) in malignant tumors. Retrocopies are duplications of genes encoding proteins that can be inserted into both exonic and intronic regions of other genes. Of the ~ 8,000 retrocopies of the human genome, ~ 2,500 are co-located in regions (intronic or exonic) of coding genes(host genes). Specifically, in this project we will analyze the level of expression and the co-expression of intragenic retrocopies and their host genes in approximately 10,000 cancer samples. We will also evaluate the implications of its insertion in altering gene expression and the formation of chimeric transcripts. For this, we will develop and use computational methodologies, looking for cases in which the deregulated transcription of the inserted retrocopy, possibly related to the tumor context, affects the rate of transcription, splicing and polyadenylation of host genes. In the end, we hope to contribute to a better understanding of the level of expression and the role of intragenic retrocopies in the process of regulating gene expression in tumors.