Transcriptos de RNAPIII en la respuesta de estrés: una hipótesis

NATALIA ESTEFANÍA CONTRERAS; GRACIELA LIDIA BOCCACCIO; MARCELO PÉREZ

Buenos Aires

Workshop; RNA Molecular and Cellular Biology Workshop; 2018

RNA society

Stress granules (SGs) are macromolecular aggregates of mRNAs and proteins that belong to a growing family of "liquid organelles". SGs are specific to the cellular stress response and form transiently upon acute stress. We performed a high-throughput RNAi screen in Drosophila cells to identify novel signaling pathways that regulate SG dynamics. Here, we focus on the role of Dusp11, an RNA-5'-triphosphate phosphatase, which negatively affects the formation of SGs. Dusp11 acts mainly on Pol III transcripts, releasing 5'pRNA and allowing 5'-3 'degradation by specific exonucleases. We used fly and mammalian cell lines, specifically HEK293T and U2OS, exposed to arsenite, a well-known model of oxidative stress, in combination with imaging and RNAi strategies. We found that Dusp11 KD increases SGs formation in both Drosophila and mammalian cells. Conversely, the overexpression of Dusp11 impairs SGs assembly. In addition, SGs formed in Dusp11 KD cells are resistant to cycloheximide, a well-known translational inhibitor that stabilizes polysomes thereby inducing SG dissolution. Dusp11 is not a major SG component. Dusp11 is mainly nuclear and forms subdomains that do not colocalize with speckles nor polyadenylated RNA clusters. We speculate that Dusp11 controls the accumulation of ncRNAs transcribed by Pol III, which directly or indirectly regulates the stress response and the formation of SGs.