Germ Cell Immortality in C. elegans: Reduced Insulin Signaling Restores Germline Immortality in PIWI Argonaute PRG-1 Mutants
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Simon, Matt. Germ Cell Immortality In C. Elegans: Reduced Insulin Signaling Restores Germline Immortality In Piwi Argonaute Prg-1 Mutants. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School, 2014. https://doi.org/10.17615/f06t-ag45APA
Simon, M. (2014). Germ Cell Immortality in C. elegans: Reduced Insulin Signaling Restores Germline Immortality in PIWI Argonaute PRG-1 Mutants. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/f06t-ag45Chicago
Simon, Matt. 2014. Germ Cell Immortality In C. Elegans: Reduced Insulin Signaling Restores Germline Immortality In Piwi Argonaute Prg-1 Mutants. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/f06t-ag45- Last Modified
- March 19, 2019
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Simon, Matt
- Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
- Abstract
- Germ cells can maintain themselves indefinitely over many generations, effectively free of the proliferative damage that affects most somatic tissues. Deficiency for the <italic>C. elegans<italic> Piwi paralog <italic>prg-1<italic> results in lineages that display normal fertility for many generations, but then become progressively sterile. Although PRG-1 represses the Tc3 transposon, data suggests that transposition-induced mutations are unlikely the cause of sterility. Instead, several lines of evidence suggest that a heritable form of stress is responsible for the degrading fertility and ultimately sterility. For example, sterile <italic>prg-1<italic> animals undergo stereotypical large-scale germline remodeling events reminiscent of starvation-induced Adult Reproductive Diapause (ARD). This remodeling depends on the DAF-16 stress response transcription factor as well as the apoptosis proteins CED-3, CED-4 and CEP-1. However, the sterility of <italic>prg-1<italic> adults can be restored by strong activation of DAF-16/Foxo via RNAi knockdown of <italic>daf-2<italic>. Furthermore, genetic mutation of daf-2 completely rescued <italic>prg-1<italic> progressive sterility. <italic>daf-2<italic> mutations elicit stress resistance in the soma and can suppress the progressive sterility of <italic>prg-1<italic> mutants via DAF-16 in a cell non-autonomous manner dependent on RDE-2, MUT-7 and PPW-1, indicating the involvement of an RNAi pathway downstream of the IGF/insulin signaling response. Transposons and tandem repeat tracts were desilenced in late generation <italic>prg-1<italic> strains, but not in <italic>prg-1; daf-2<italic> double mutants. We found that two histone demethylases, SPR-5 and RBR-2, are required for the rescue of <italic>prg-1<italic> by <italic>daf-2<italic>. Further, reduced insulin/IGF1 signaling restored levels of 22G siRNAs that target repetitive loci in <italic>prg-1<italic> mutants. Thus, the germ cell-specific Piwi/PRG-1 small RNA pathway represses a heritable form of toxic stress that can be repressed by <italic>daf-2<italic>-mediated DAF-16 activity. We propose that deficiency for Piwi/piRNAs functions in germ cells to suppress a source of proliferative aging linked to chromatin misregulation to insure germline integrity and progeny fitness.
- Date of publication
- August 2014
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- In Copyright
- Advisor
- Ahmed, Shawn
- Reiner, David
- Goldstein, Bob
- Bloom, Kerry
- Sekelsky, Jeff
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2014
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- Place of publication
- Chapel Hill, NC
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- There are no restrictions to this item.
- Date uploaded
- April 22, 2015
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