Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60
- Max Planck Institute for Biology of Ageing, Germany
- University of Cologne, Germany
- University of South Australia, Australia
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.
Data availability
RNA-seq data has been deposited in GEO. Accession code GSE141097.
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Evolutionarily Conserved Regulation of Immunity by the Splicing Factor RNP-6/PUF60NCBI Gene Expression Omnibus, GSE141097.
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Author details
Funding
Max-Planck-Gesellschaft
- Chun Kew
- Wenming Huang
- Adam Antebi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Kew et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60
eLife 9:e57591.
https://doi.org/10.7554/eLife.57591
