Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32538777.
- Also identified by DOI 10.7554/eLife.57591 and PMC identifier 7332298.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>C. elegans</i>, 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 <i>rnp-6</i> dependent manner, and <i>rnp-6</i> 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.
Medical subject headings
- Caenorhabditis elegans
- Immunity, Innate
- RNA Splicing Factors
- Repressor Proteins