Rege-1 promotes C. elegans survival by modulating IIS and TOR pathways

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Metabolic pathways regulate physiological responses to environmental cues.
• Tight control of these responses is essential for organismal homeostasis.
• The ribonuclease REGE-1's role in stress response is not fully understood.

Purpose of the Study:

• To investigate the function of the ribonuclease REGE-1 in Caenorhabditis elegans.
• To elucidate the molecular mechanisms by which REGE-1 regulates survival upon pathogen challenge.
• To identify the metabolic pathways influenced by REGE-1 activity.

Main Methods:

• Caenorhabditis elegans stress response assays.
• RNA sequencing (mRNA-seq) for global gene expression analysis.
• Chromatin immunoprecipitation (ChIP) data analysis and gene deletion studies.

Main Results:

• Defective REGE-1 ribonuclease activity causes early death in C. elegans upon Pseudomonas aeruginosa infection, dependent on the transcription factor ets-4.
• REGE-1 regulates the insulin/IGF signaling (IIS) and target of rapamycin (TOR) kinase pathways.
• Dysregulation of ets-4 mRNA degradation in rege-1 mutants leads to upregulation of class II longevity genes and activation of TORC1 signaling, contributing to poor survival.

Conclusions:

• REGE-1 is critical for C. elegans survival by tightly regulating physiological responses to environmental stimuli, particularly pathogen exposure.
• REGE-1's function in controlling ets-4 mRNA and downstream metabolic pathways, including IIS and TOR, is essential for preventing premature death.
• The findings highlight REGE-1's conserved role, similar to its mammalian ortholog Regnase-1, in modulating stress responses and metabolic signaling.