Identification of karyopherins involved in the nuclear import of exosome subunits in Saccharomyces cerevisiae

• Grant number: 22/00071-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): August 01, 2022
• Effective date (End): July 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Carla Columbano de Oliveira
• Grantee: Valdir Gomes Neto
• 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
• Associated scholarship(s): 22/16740-2 - Understanding the mechanism of the RNA Exosome subunits nuclear transport in Saccharomyces cerevisiae, BE.EP.PD

Abstract

The exosome complex is one of the most versatile RNA degradation machineries ineukaryotes. It plays an important role in the biogenesis of various RNAs (rRNAs, snoRNAs, snRNAs, ncRNAs) and in the regulation of specific mRNA expression. levels both in the nucleus and cytoplasm. The exosome acts at various stages ofRNA processing and degradation and has 3'-5' exoribonucleolytic activity involved inthe processing and degradation of all types of RNA. In eukaryotes, the exosome canvary in composition and mode of action depending on its location in the cell and canhave different substrates: the nuclear exosome is involved in the maturation of various RNAs and in the degradation of unstable pre-mRNAs. In the cytoplasm, the exosome is involved in the control of mRNA levels in the cell, and in the degradation of aberrant mRNAs. The exosome complex is formed by ten subunits in the cytoplasm (Exo10) and eleven subunits in the nucleus (Exo11). Of the eleven subunits, only Rrp6 (exclusively in the nucleus) and Rrp44 have catalytic activity and each bind to opposite sides of the core of the complex. In the cytoplasm, the exosome interacts with the Ski complex via Ski7 to recognize and degrade aberrante RNAs. In the nucleus, the exosome is highly concentrated in the nucleolus, where pre-rRNA is transcribed and processing begins. Although the function of the exosome has been extensively studied, there is no detailed knowledge of the mechanisms of transport into the nucleus or retention in the cytoplasm. This project proposes to investigate the transport of the exosome to the nucleus by identifying the karyopherins responsible for this process and to explore the importance of the Skicomplex in maintaining the exosome in the cytoplasm, using the yeast Saccharomyces cerevisiae as a model eukaryote for these studies. (AU)