論文 - 詳細
| RRC ID | 88158 |
|---|---|
| 著者 | Ewe CK, Teichman G, Weiss S, Knott MML, Anava S, Gingold H, Sarmiento MB, Troemel E, Rechavi O. |
| タイトル | Dynamic control of Argonautes by a rapidly evolving immunological switch. |
| ジャーナル | Curr Biol |
| 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. |
| 巻・号 | 35(13) |
| ページ | 3076-3089.e5 |
| 公開日 | 2025-7-7 |
| DOI | 10.1016/j.cub.2025.05.039 |
| PII | S0960-9822(25)00655-4 |
| PMID | 40494360 |
| PMC | PMC12401492 |
| MeSH | Animals Argonaute Proteins* / genetics Argonaute Proteins* / immunology Argonaute Proteins* / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / immunology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / immunology Caenorhabditis elegans Proteins* / metabolism RNA Interference |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm1673 tm894 tm1200 tm1116 tm1860 |