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An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress
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Journal Article
An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress
2024
Overview
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.
In this study, Vergani-Junior
et al
. show that increased expression of the argonaute ALG-1 in long-lived worms improves oxidative stress resistance through the modulation of microRNAs that downregulate the protein disulfide isomerase pathway.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/39
/ 38/89
/ 38/91
/ 64/11
/ Animals
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - metabolism
/ Glucagon-Like Peptide 1 - metabolism
/ Humanities and Social Sciences
/ Humans
/ miRNA
/ Mutants
/ Oxidants
/ Proteins
/ RNA
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Science
