ArticleCurrent biology : CB2025
Dynamic control of Argonautes by a rapidly evolving immunological switch.
Article in Current biology : CB, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Reduced insulin/IGF-1 signaling and loss ofmicroPublication biology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
Small RNAs (sRNAs), coupled with Argonaute proteins (AGOs), regulate diverse biological processes, including immunity against nucleic acid parasites. C. elegans possesses an expanded repertoire of at least 19 AGOs functioning in an intricate gene regulatory network (GRN). However, the regulation of AGOs and how their functions adapt to genetic or environmental perturbations remains incompletely understood. Here, we report that PALS-22, a member of an unusually expanded protein family in C. elegans, acts as a negative regulator of antiviral RNAi involving the RIG-I homolog. Loss of pals-22 enhances the silencing of transgenes and endogenous double-stranded RNAs (dsRNAs). We found that PALS-22 normally suppresses the expression of two AGOs, VSRA-1 and SAGO-2, which are activated by the bZIP transcription factor ZIP-1. When pals-22 is eliminated, vsra-1 and sago-2 are upregulated. These AGOs, in turn, play key roles in defense against foreign genetic elements and intracellular pathogens, respectively. Surprisingly, although immune genes functioning in the intracellular pathogen response (IPR) are upregulated in pals-22 mutants, removing SAGO-2 or the RNA-dependent RNA polymerase RRF-3 in these mutants downregulates these genes. This observation appears to contrast with the typical gene-silencing role of small interfering RNAs (siRNAs). Finally, the analysis of C. elegans wild isolates and lab reference strains reveals that PALS-22 regulates several germline AGOs, affecting germline mortality and transgenerational epigenetic inheritance. In summary, PALS-22 is a key genetic node that balances the trade-off between immunity and germline health by modulating the functions of different AGOs, thereby shaping the outputs of the RNAi machinery and the dynamics of epigenetic inheritance.
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Registered trials
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