An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress

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Abstract

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 show that upregulation of 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.

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Vergani-Junior, C. A., Moro, R. D. P., Pinto, S., De-Souza, E. A., Camara, H., Braga, D. L., … Mori, M. A. (2024). An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-47306-4

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