SERBP1 in a retrotransposition context: Study of L1 interactions and their functional impact

• Grant number: 24/22059-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Julia Leite Cordeiro de Souza
• Supervisor: John Lacava
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Rockefeller University, United States
• Associated to the scholarship: 22/04962-0 - Study of the oncoprotein SERBP1: analysis of its transcriptome, proteome and functions of the wildtype version and point mutations identified in cancer., BP.DR

Abstract

Retrotransposons are mobile genetic elements that copy their sequences and insert them in new genomic location through RNA intermediates using a "copy and paste" mechanism called retrotransposition. Long-Interspersed Element-1 (L1) is the only autonomous functional retrotransposon in humans. When L1 is transcript, two proteins are translated: ORF1p and ORF2p, in the cytosol they can form a ribonucleoprotein complex that can associates with other molecules such as RNA binding proteins. In this context, SERBP1, an mRNA binding protein is associated with many cellular events such as chromatin remodeling, mRNA stability, and stress granules clearance. Previous data revealed an association between L1 and SERBP1 and its RNA, and a possible colocalization in granules. However, these interactions remain unclear and controversial. Besides that, those previous studies considered only ectopic expressions to analyze the interaction between SERBP1 and L1 and its transcripts. Here, we propose to investigate the involvement of SERBP1 and retrotransposition analyzing endogenous interactions between SERBP1 and L1 at a protein level through IP-MS and at a transcript level through RIP-seq in two cancer cell lines. Considering that both SERBP1 and ORF1p are expressed in granules, we will analyze the endogenous colocalization of them and other granules markers through an immunofluorescence assay. After performing these experiments, we will be able to determine how these molecules are related and choose the proper functional assays to elucidate the biological role of SERBP1 and L1.