DUSP12 as a potential RNA-binding phosphatase: investigating its RNA targets and interactions with NAT10 and TCOF1 under stress conditions in glioblastoma

• Grant number: 25/03838-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 31, 2025
• End date: October 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Fábio Luis Forti
• Grantee: Viktor Kalbermatter Boell
• Supervisor: Isaac Alexander Chaim
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 22/13414-7 - Characterization of the involvement of DUSP12 and its nuclear targets in the response of hepatic cell models to genotoxic stress, BP.DR

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor, with poor prognosis due to resistance to genotoxic therapies like temozolomide and ionizing radiation. The DNA damage response (DDR) is central to therapy resistance, and RNA-binding proteins (RBPs) have emerged as key regulators of DDR by modulating mRNA stability, translation, and repair protein recruitment. Additionally, nucleolar stress and ribosome biogenesis (RB) are increasingly recognized as cellular processes that can trigger DDR signaling. Dual-specificity phosphatase 12 (DUSP12) has been identified as a potential RBP interacting with key nucleolar proteins NAT10 and TCOF1, both implicated in DDR and RB. This project aims to characterize DUSP12 as an RBP in human glioblastoma models, assess its RNA interactions under genotoxic, nucleolar, and oxidative stress, and determine its role in regulating NAT10 and TCOF1 activity. Enhanced crosslinking and immunoprecipitation (eCLIP) will be employed to identify DUSP12-associated RNAs, while CRISPR/Cas9-mediated DUSP12 knockout will elucidate its functional impact on DDR signaling and ribosome biogenesis together with NAT10 and TCOF1 partners. Understanding DUSP12's role may uncover novel RNA-centric therapeutic targets to overcome glioblastoma's resistance to genotoxic therapies. In this context, Professor Chaim's research group stands out as a strong candidate for this research internship, as it focuses on the study of RBPs in the DNA damage response and employs advanced experimental methodologies that are currently not available in Brazil. (AU)