Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
- Princeton University, United States
- Stanford University, United States
Abstract
C. elegans lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males' hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize.
Data availability
Microarray data are available at the following links:"L4 fog-2(q71) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7332"L4 fem-3(q20) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7333"D3 mated fog-2(q71) vs pqm-1(ok485) hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7334
Article and author information
Author details
Funding
NIH Office of the Director (Pioneer 1DP1OD020400-01)
- Coleen T Murphy
Glenn Foundation for Medical Research (NA)
- Coleen T Murphy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Shi 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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Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
eLife 8:e46413.
https://doi.org/10.7554/eLife.46413
Further reading
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- Evolutionary Biology
- Genetics and Genomics
Young Caenorhabditis elegans hermaphrodites use their own sperm to protect against the negative consequences of mating.
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- Genetics and Genomics
RNA-binding proteins (RBPs) perform diverse functions including the regulation of chromatin dynamics and the coupling of transcription with RNA processing. However, our understanding of their actions in mammalian neurons remains limited. Using affinity purification, yeast-two-hybrid and proximity ligation assays, we identified interactions of multiple RBPs with neural retina leucine (NRL) zipper, a Maf-family transcription factor critical for retinal rod photoreceptor development and function. In addition to splicing, many NRL-interacting RBPs are associated with R-loops, which form during transcription and increase during photoreceptor maturation. Focusing on DHX9 RNA helicase, we demonstrate that its expression is modulated by NRL and that the NRL–DHX9 interaction is positively influenced by R-loops. ssDRIP-Seq analysis reveals both stranded and unstranded R-loops at distinct genomic elements, characterized by active and inactive epigenetic signatures and enriched at neuronal genes. NRL binds to both types of R-loops, suggesting an epigenetically independent function. Our findings suggest additional functions of NRL during transcription and highlight complex interactions among transcription factors, RBPs, and R-loops in regulating photoreceptor gene expression in the mammalian retina.
