Investigation of PIMREG participation in mRNA splicing in glioblastoma cells.

• Grant number: 25/11800-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Leticia Fröhlich Archangelo
• Grantee: Lígia Arantes Sardinha
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glioblastoma (GBM) is the most common central nervous system tumour in adults, often associated with genetic heritance and irradiation exposure. It is classified as grade 4 for malignancy because of its survival levels after five years in only 6% of the patients. The protein PIMREG (PICALM interacting mitotic regulator) - an important biomarker for cell proliferation and tumour progression - is overexpressed in a variety of cancer types, presenting higher levels in GBM, besides being previously associated to DNA damage response, which suggests its interference in treatment resistance. PIMREG is aim of splicing regulator kinase, UHMK1, which presents UHM domain, a common interactor with splicing factors. Splicing is a physiological process that is often altered in tumours, which forms aberrant RNAs that originate protein isoforms that can activate oncogenes or inhibit tumour suppressors, contributing to tumorigenesis. Recent proteomics analysis of our group revealed that PIMREG interacts with many splicing factors, including the main substrate of UHMK1, splicing factor 1 (SF1), suggesting the PIMREG participation in the mRNA processing. Therefore, the important role of mRNA processing in tumour development and the high levels of PIMREG in GBM make it indispensable to study its probable participation in splicing. In that way, this project aims to evaluate the PIMREG participation in mRNA processing, by means of validation of the proteomics results, about the PIMREG-SF1 interaction, using co-immunoprecipitation and subcellular co-localization, besides the investigation of PIMREG participation in reporter gene splicing.