Structural and biochemical characterization of stress granules assembly: The ins and outs of translation

• Grant number: 13/21796-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2014
• Status: Discontinued
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fernanda Canduri
• Grantee: Reetesh Kumar
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated scholarship(s): 15/07263-2 - Physicochemical characterization and protein-protein interaction analysis between pab1, pbp1 and pbp4 of stress granule assembly, BE.EP.PD

Abstract

The flow of genetic information in all cells progresses from DNA to messenger RNA (mRNA) to protein. Many events have to occur precisely to generate the protein product accurately and efficiently. Among these, reversible translational repression and mRNA decay now appear as highly regulated processes that allow cells to rapidly modify protein production in response to environmental factors. In this context, cytoplasmic stress granules (SGs) play a very active role as they allow for the storage of translationally inactive mRNAs awaiting either degradation or release of translation inhibition and thereby appear to be required to allow optimal translation of stress-responsive mRNAs. To understand the control of gene expression, it is thus necessary to unravel the regulation and mechanisms of both translation repression and mRNA degradation/storage.The aim of this proposal is to improve our understanding of the mechanisms underlying SGs assembly, especially the Pbp1, Pbp4 and Pab1 proteins. In particular, we will focus on the molecular basis and dynamics of the protein complexes and networks involved in the assembly of these foci and analyze the effects of post-translational events (e.g. phosphorylation, methylation, etc.).The investigation of the protein complexes involved in SGs assembly will strongly improve our understanding of the control of mRNA storage, but will also provide novel insights into the mechanisms of translational repression. Similarly, insights into the regulation of mRNA storage will connect this process to events experienced by eukaryotic cells during cell cycle or following stress exposure such as toxic agents, pollution, nutrient starvation, etc.