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Abstract BackgroundIn all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking. ResultsHere, by analyzingadr-1andadr-2null mutants in well-established slow-killing assays, we find that bothCaenorhabditis elegansADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans. Furthermore, our high-throughput sequencing and genetic analysis reveal that ADR-1 and ADR-2 function in the same pathway to regulate collagen expression. Consistent with this finding, our scanning electron microscopy studies indicateadr-1;adr-2mutant animals also have altered cuticle morphology prior to pathogen exposure. ConclusionsOur data uncover a critical role of theC. elegansADAR family of RNA-binding proteins in promoting cuticular collagen expression, which represents a new post-transcriptional regulatory node that influences the extracellular matrix. In addition, we provide the first evidence that ADAR mutant animals have altered susceptibility to infection with several opportunistic human pathogens, suggesting a broader role of ADARs in altering physical barriers to infection to influence innate immunity.
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ADAR-mediated regulation of PQM-1 expression in neurons impacts gene expression throughout C. elegans and regulates survival from hypoxia
The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal’s surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues. The transcription factor PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as impacting survival from hypoxia. Herein, we reveal a novel mechanism for regulating PQM-1 expression specifically in neural cells of larval animals. Our studies reveal that the RNA-binding protein (RBP), ADR-1, binds topqm-1mRNA in neural cells. This binding is regulated by the presence of a second RBP, ADR-2, which when absent leads to reduced expression of bothpqm-1and downstream PQM-1 activated genes. Interestingly, we find that neuralpqm-1expression is sufficient to impact gene expression throughout the animal and affect survival from hypoxia, phenotypes that we also observe inadrmutant animals. Together, these studies reveal an important posttranscriptional gene regulatory mechanism inCaenorhabditis elegansthat allows the nervous system to sense and respond to environmental conditions to promote organismal survival from hypoxia.
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- Award ID(s):
- 1917050
- PAR ID:
- 10531743
- Editor(s):
- Gilbert, Wendy V
- Publisher / Repository:
- PLoS Biology
- Date Published:
- Journal Name:
- PLOS Biology
- Volume:
- 21
- Issue:
- 9
- ISSN:
- 1545-7885
- Page Range / eLocation ID:
- e3002150
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pbio.3002150
