Max Planck Institute for Biology of Ageing, Cologne, Germany
Julia Fischer
Department I of Internal Medicine, University of Cologne, Cologne, Germany; Division of Infectious Diseases, University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Cologne, Germany
Raja Ganesan
Cellular-Stress and Immune Response Laboratory, Centre for Cancer Biology, University of South Australia, Adelaide, Australia
Max Planck Institute for Biology of Ageing, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in C. elegans, we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner, and rnp-6 gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/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, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.
