Characterization of the role of the exoxome subunity DIS3 in the control of cell cycle

• Grant number: 24/02036-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• End date: April 30, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Columbano de Oliveira
• Grantee: Katherine Tsantarlis
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/00901-1 - Posttranscriptional control of gene expression: pre-rRNA processing, mRNA degradation, splicing and snoRNP assembly in Saccharomyces cerevisiae, AP.TEM

Abstract

The RNA exosome is a multisubunit complex responsible for processing and degradation of all classes of RNA. This eukaryotic complex is present in nucleus and cytoplasm, and formed by eleven protein subunits, two of them, catalytically active. In humans, the catalytic subunit DIS3 is also associated with control of cell cycle, and inhibition of its function, caused by mutations in its exoribonuclease domain, can lead to defects in mitosis. Some of the exosome subunits have been shown to associate with the chromatin, and with the control of the cell cycle in yeast and Drosophila melanogaster. Exosome disfunction has also been associated with human diseases, including cancer. This proposal aims to determine the subcellular localization and function of the exosome subunits during cell cycle, using the glioblastoma cells U87MG as a model system. To achieve these goals, molecular biology methods and immunofluorescence assays will be used to understand the effect of DIS3 knockdown in the progression of cell cycle, in the exosome localization and in cell viability. (AU)