Biology subjects

Gabaldon, C.

Publications and source records attributed to Gabaldon, C..

2 recordsLinked to original sources

bioRxiv2026

LIN-23 Affects C. elegans Pathogen and Stress Resistance by Modulating SKN-1 Activity

During pathogen infection, the C. elegans transcription factor SKN-1 is activated through the p38 MAPK cascade to protect against oxidative damage and promote host survival. SKN-1, the functional ortholog of the mammalian Nrf family of transcription factors, participates in various biological processes and is subject to complex regulation. In this study, we identify a previously unrecognized role for LIN-23 in regulating SKN-1 during adult stress conditions. LIN-23 is an F-box protein that functions as the substrate recognition component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex and has been implicated in diverse cellular processes, including cell cycle regulation, neurite outgrowth, and centrosome duplication. Although LIN-23 has previously been reported to negatively regulate SKN-1 in other contexts, our findings demonstrate that during pathogen exposure, LIN-23 acts as a positive regulator of SKN-1 activity. Specifically, loss of LIN-23 reduced SKN-1 activity and decreased survival of infected adult animals. Having established this novel relationship between LIN-23 and SKN-1, we investigated the mechanism by which LIN-23 regulates SKN-1 activity. Because SKN-1 activation occurs via the p38 MAPK signaling pathway, followed by nuclear localization, we examined whether LIN-23 influences these events, but observed no decrease in p38 MAPK phosphorylation or SKN-1 nuclear localization. Instead, we provide evidence that LIN-23 function is dependent on WDR-23, a well-established negative regulator of SKN-1. A model is proposed in which LIN-23 promotes SKN-1 activity by targeting nuclear WDR-23 for degradation. SUMMARYSKN-1 is a C. elegans transcription factor and the ortholog of mammalian Nrf proteins. Under oxidative stress conditions, including those induced by infection, SKN-1 plays a protective role. Since SKN-1 regulation is complex, understanding the mechanisms that modulate its activity is important for defining stress response pathways. The authors demonstrate that the F-box protein LIN-23 functions as a positive regulator of SKN-1. Their genetic analyses indicate that LIN-23 does not influence the canonical SKN-1 activation cascade. Instead, LIN-23 appears to regulate SKN-1 activity by modulating a negative regulator, WDR-23.

genetics↗

bioRxiv2020

Intergenerational pathogen-induced diapause in C. elegans is modulated by mir-243.

The interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNAi machinery, suggesting the involvement of sRNAs as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small non-coding RNAs, we found that mir-243-3p is the only transcript continuously upregulated in animals exposed to both, P. aeruginosa or S. enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small non-coding RNA in the intergenerational defensive response against pathogenic bacteria and inter-kingdom communication. ImportancePersistent infection of the bacterivore nematode C. elegans with bacteria such as P. aeruginosa and S. enterica makes the worm diapause or hibernate. By doing this, the worm closes its mouth avoiding infection. This response takes two generations to be implemented. In this work, we looked for genes expressed upon infection that could mediate the worm diapause triggered by pathogens. We identify mir-243-3p as the only transcript commonly upregulated when animals feed on P. aeruginosa and S. enterica for two consecutive generations. Moreover, we demonstrate that mir-243-3p is required for pathogen-induced dauer formation, a new function that has not been previously described for this miRNA. We also find that the transcriptional activators DAF-16, PQM-1 and CRH-2 are necessary for the expression of mir-243 under pathogenesis. Here we establish a relationship between a small RNA and a developmental change that ensures the survival of a percentage of the progeny.

microbiology↗