Project A03 - Post-transcriptional gene regulation in T cell activation, effector function and memory formation

With the funding from this CRC our lab has studied the functions of RNA-binding proteins (RBPs) Roquin-1, Roquin-2 and Regnase-1 in T cells to uncover that Roquin and Regnase-1 proteins are physically interacting and functionally cooperating to prevent the development of autoimmunity. In the next funding period we will inspect the process and consequences of Roquin and Regnase-1 cleavage by the MALT1 paracaspase and analyze Crispr/Cas9 gene-edited mouse models that replace the Roquin-1 and Roquin-2 proteins with mutant versions that are insensitive to MALT1 cleavage or introduce a mutation into Roquin-1 that interferes with its binding to Regnase-1. We will ask how these genetic alterations change T cell homeostasis, induce gene expression changes in naïve T cells and impact on T cell differentiation or T cell help to B cells, class switch recombination and autoantibody formation or how the different mutant mice respond to viral infections. Together, these analyses shall close important current gaps in our understanding of how MALT1, Roquin and Regnase-1 control cellular programs of T cell activation, effector function, exhaustion and memory formation.