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キーワード:
Alternative Splicing
Animals
Anti-Inflammatory Agents
Bacterial Infections/metabolism
Caenorhabditis elegans/*metabolism/microbiology
Caenorhabditis elegans Proteins/metabolism
Escherichia coli
Gene Expression
HeLa Cells
Humans
*Immunity, Innate
Longevity/genetics
Male
Mice
Mitogen-Activated Protein Kinases/metabolism
RAW 264.7 Cells
RNA Splicing Factors/*metabolism
RNA, Messenger/metabolism
Repressor Proteins/*metabolism
Signal Transduction
Staphylococcus aureus
*C. elegans
*ageing
*genetics
*genomics
*immunology
*inflammation
*innate immunity
*splicing
要旨:
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.
