Rebekah Napier-Jameson: RNA binding proteins coordinately control lifespan in C. elegans

In order to identify genes that coordinately control gene expression with important phenotypic consequences, we performed a CRISPR/Cas-9 based Synthetic Genetic Interaction (CRISPR-SGI) screen in C. elegans. We focused on conserved neuronally-expressed RNA binding proteins, and identified many double mutants with unexpected fitness defects. In one notable interaction between the MBNL1/2 ortholog mbl-1 and the ELAVL ortholog exc-7, double mutants displayed a severely shortened lifespan (~70% decrease). We have used RNA-Seq data to investigate which RNAs may be uniquely dysregulated in the double mutant. nhx-6, a predicted Na/H exchanger, which was identified from our RNA Seq data contributes to the phenotype and is expressed in the intestine. mbl-1 and exc-7 are neuronally-enriched genes. Initial experiments have shown partial rescue of the lifespan phenotype with mbl-1 re-expression in the nervous or intestinal tissues of the double mutant but not muscle tissue. Shortly we will be conducting experiments to test whether exc-7 expression in the nervous system is the critical tissue affecting whole-worm lifespan. Through these studies we hope to identify how these RNA binding proteins are contributing to the lifespan phenotype seen in the mbl-1;exc-7 double mutants.