RRC ID 65252
Author Kew C, Huang W, Fischer J, Ganesan R, Robinson N, Antebi A.
Title Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60.
Journal Elife
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.
Volume 9
Published 2020-6-15
DOI 10.7554/eLife.57591
PII 57591
PMID 32538777
PMC PMC7332298
MeSH Alternative Splicing Animals Anti-Inflammatory Agents Bacterial Infections / metabolism Caenorhabditis elegans / metabolism* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / metabolism DNA-Binding 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
Resource
C.elegans tm3036 tm1978