BioProject

Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. More...

Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. ALG-1, the C. elegans ortholog of human AGO2, plays an essential role in microRNA processing and function. Here we investigated the mechanisms governing ALG-1 expression in C. elegans and the players controlling lifespan and stress resistance downstream of ALG-1. We found that upregulated ALG-1 is a shared feature in conditions linked to increased longevity (e.g., germline-deficient glp-1 mutants). ALG-1 knockdown reduces lifespan and oxidative stress resistance, while overexpression enhances survival against pro-oxidant agents but not heat or reductive stress. R02D3.7 represses alg-1 expression, impacting oxidative stress resistance at least in part via ALG-1. microRNAs upregulated in glp-1 mutants (miR-87-3p, miR-230-3p, and miR-235-3p) can target genes in the protein disulfide isomerase pathway and protect against oxidative stress. This study unveils a tightly regulated network involving transcription factors and microRNAs which controls organisms’ ability to withstand oxidative stress. Overall design: To investigate the role of specific miRNAs in oxidative stress resistance in long-lived worms, we examined the miRNA expression profiles in C. elegans strains with either alg-1 overexpression (ALG-1 O/E) or the glp-1(e2144) mutation. We conducted gene expression profiling analysis using data obtained from small RNA-seq, which was enriched for miRNAs, from four different strains. The comparative gene expression profiling analysis included the wild type (WT) strain and the germline-less longevity (glp-1 mutant) strain, as well as animals with alg-1 overexpression (ALG-1 O/E) and its control (CT20) strain. Less...