Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60.

ELife
Chun KewAdam Antebi

Abstract

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.

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Methods Mentioned

BETA
immunoprecipitation
co-immunoprecipitation
transfection
transfections
PCR
Assay
PCRs
electrophoresis
Protein Assay
FCS

Software Mentioned

stringtie
DAVID ( Database for Annotation , Visualization and Integrated...
SAJR
MiModD
KISSDE
Cufflinks

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