Understanding the link between splicing and mRNA localization by structural biology

• Applicant: Professorin Dr. Teresa Carlomagno
• Subject Area: Structural Biology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 355518810

mRNA localization is essential to all developmental programmes, such as cell movement, cell specialization and asymmetric cell division. In Drosophila melanogaster, oskar mRNA localization to the posterior pole of the oocyte determines where the abdomen and primordial germ cells form. The transport requires the recognition of specific sequences in the oskar mRNA transcript by trans acting factors. These ribonucleoprotein particles then interact with the kinesin motor for transport along the microtubules. The SOLE RNA is a specific oskar mRNA sequence that forms upon splicing and is located only a few nucleotides away from the Exon Junction Complex (EJC) deposition site. Both the SOLE RNA and the EJC are indispensable for mRNA localization.PYM (Partner of Y14-Mago) is a protein that was identified because of its association with the core components of the EJC Y14 and Mago. PYM has a dual role in both EJC homeostasis and mRNA localization. Recently we discovered that the protein directly interacts with the SOLE RNA, suggesting that mRNA localization and EJC homeostasis might be co-regulated.In this grant proposal we aim at shedding light on the role of the SOLE RNA and PYM in mRNA localization, as well as their interplay with the EJC. We will take an interdisciplinary approach combining structural biology, functional assays in vivo and biochemistry.This project will contribute to the molecular understanding of one of the most regulated, complex and fundamental processes of organism development.

• DFG Programme: Research Grants