Dynamic control of Argonautes by a rapidly evolving immunological switch
Bibliographic record
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".