Evolutionarily Conserved Regulation of Immunity by the Splicing Factor RNP-6/PUF60
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ABSTRACT: Splicing is a vital cellular process that modulates important aspects of animal physiology, including metabolism and lifespan. From a cold stress screen, we identified a novel mutant of the splicing factor RNP-6/PUF60, which evokes resistance to various abiotic stresses, yet is highly sensitive to pathogenic bacterial challenge. Molecular and genetic experiments reveal that RNP-6 suppresses immunity, but promotes animal longevity, suggesting a tradeoff between these processes. Pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. Genetic epistasis and biochemical experiments reveal that RNP-6 acts through PMK-1 MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells. Our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE141097 | GEO | 2020/07/02
REPOSITORIES: GEO
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