An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress.
Carlos Alberto VerganiRaíssa De P MoroSilas Pinto SilvaEvandro A De-SouzaHenrique CamaraDeisi L BragaGuilherme Tonon-da-SilvaThiago L KnittelGabriel P RuizRaissa G LudwigKatlin B MassirerWilliam B MairMarcelo Alves da Silva MoriPublished in: Nature communications (2024)
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.
Keyphrases
- oxidative stress
- poor prognosis
- dna damage
- transcription factor
- diabetic rats
- ischemia reperfusion injury
- induced apoptosis
- healthcare
- public health
- cell proliferation
- endothelial cells
- binding protein
- machine learning
- gene expression
- heat stress
- dna repair
- signaling pathway
- deep learning
- long non coding rna
- heat shock
- health information
- risk assessment
- wild type