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| Status |
Public on Dec 06, 2023 |
| Title |
A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI [ChIP-seq] |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Coordination of cellular responses to stress are essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here we identify how SKN-1 activation in two ciliated ASI neurons in C. elegans results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues. An increase in the expression of established SKN-1 stress response and lipid metabolism gene classes of RNA in the ASI neurons, in addition to the increased expression of several classes of non-coding RNA, define a molecular signature of animals with constitutive SKN-1 activation and diminished healthspan. We reveal neddylation as a novel regulator of the SKN-1 homeostat that mediates SKN-1 abundance within intestinal cells. Moreover, RNAi-independent activity of the dicer-related DExD/H-box helicase, drh-1, in the intestine, can oppose the effects of aberrant SKN-1 transcriptional activation and delays age-dependent decline in health. Taken together, our results uncover a cell non-autonomous circuit to maintain organism-level homeostasis in response to excessive SKN-1 transcriptional activity in the sensory nervous system.
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| Overall design |
ChIPseq of wildtype and SKN-1gf GFP to asses the genomic binding profiles of each variant of the SKN-1 transcription factor
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| Contributor(s) |
Turner C, Stuhr N, Ramos C, Van Camp B, Curran S |
| Citation missing |
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| |
| Submission date |
Oct 27, 2023 |
| Last update date |
Dec 07, 2023 |
| Contact name |
Chris Turner |
| E-mail(s) |
cdturner@usc.edu
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| Organization name |
University of Southern California
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| Street address |
3715 McClintock Ave
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90089 |
| Country |
USA |
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| Platforms (1) |
| GPL22765 |
Illumina HiSeq 4000 (Caenorhabditis elegans) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE246467 |
A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI neurons. |
|
| Relations |
| BioProject |
PRJNA1032975 |
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