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.
Article and author information
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.
Reviewing Editor
- Bruno Lemaître, École Polytechnique Fédérale de Lausanne, Switzerland
Publication history
- Received: April 6, 2020
- Accepted: June 14, 2020
- Accepted Manuscript published: June 15, 2020 (version 1)
- Version of Record published: July 2, 2020 (version 2)
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
Further reading
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- Genetics and Genomics
- Medicine
Background:
De novo mutations underlie individually rare but collectively common pediatric congenital disorders. Some of these mutations can also be detected in tissues and from cells in a parent, where their abundance and tissue distribution can be measured. We previously reported that a subset of these mutations is detectable in sperm from the father, predicted to impact the health of offspring.
Methods:
As a cohort study, in three independent couples undergoing in vitro fertilization, we first identified male gonadal mosaicism through deep whole genome sequencing. We then confirmed variants and assessed their transmission to preimplantation blastocysts (32 total) through targeted ultra-deep genotyping.
Results:
Across 55 gonadal mosaic variants, 15 were transmitted to blastocysts for a total of 19 transmission events. This represented an overall predictable but slight undertransmission based upon the measured mutational abundance in sperm. We replicated this conclusion in an independent, previously published family-based cohort.
Conclusions:
Unbiased preimplantation genetic testing for gonadal mosaicism may represent a feasible approach to reduce the transmission of potentially harmful de novo mutations. This—in turn—could help to reduce their impact on miscarriages and pediatric disease.
Funding:
No external funding was received for this work.
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- Evolutionary Biology
- Genetics and Genomics
Hybridization is a major evolutionary force that can erode genetic differentiation between species, whereas reproductive isolation maintains such differentiation. In studying a hybrid zone between the swallowtail butterflies Papilio syfanius and Papilio maackii (Lepidoptera: Papilionidae), we made the unexpected discovery that genomic substitution rates are unequal between the parental species. This phenomenon creates a novel process in hybridization, where genomic regions most affected by gene flow evolve at similar rates between species, while genomic regions with strong reproductive isolation evolve at species-specific rates. Thus, hybridization mixes evolutionary rates in a way similar to its effect on genetic ancestry. Using coalescent theory, we show that the rate-mixing process provides distinct information about levels of gene flow across different parts of genomes, and the degree of rate-mixing can be predicted quantitatively from relative sequence divergence () between the hybridizing species at equilibrium. Overall, we demonstrate that reproductive isolation maintains not only genomic differentiation, but also the rate at which differentiation accumulates. Thus, asymmetric rates of evolution provide an additional signature of loci involved in reproductive isolation.
