Faculty Opinions recommendation of Function, targets, and evolution of Caenorhabditis elegans piRNAs.
Bibliographic record
Abstract
Piwi-interacting RNAs (piRNAs) are small RNAs required to maintain germline integrity and fertility but their mechanism of action is poorly understood.Here we demonstrate that C. elegans piRNAs silence transcripts in trans through imperfectly complementary sites.Target silencing is independent of Piwi endonuclease activity or "slicing".Instead, piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response.Endogenous proteincoding gene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are de-repressed in Piwi mutants.Genomic loci of piRNA biogenesis are depleted of protein-coding genes and tend to overlap the start and end of transposons in sense and antisense, respectively.Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements.Thus, piRNAs provide heritable, sequence-specific triggers for RNAi in C. elegans.The Piwi/piRNA pathway has an evolutionarily conserved role in germline transposon silencing in animals.C. elegans encodes two Piwi family proteins, PRG-1 and PRG-2, although PRG-2 has likely little or no function (1, 2).PRG-1 and piRNA expression is restricted to the male and female germline.The piRNAs of C. elegans are 21 nucleotides in length with a 5′ uracil (21U-RNAs) (1-4).In C. elegans piRNAs have a sequence motif, situated ~40 bp upstream of each piRNA locus, that is thought to be required for piRNA biogenesis (2, 3).A challenge in the field is to understand the mechanism(s) by which piRNAs act on their targets.Proposed functions for Piwi/piRNA complexes include the RNAi-like slicing of RNA transcripts (5-7), transcript deadenylation (8) and de novo DNA methylation (9, 10).Here we identify the targeting mechanism and the endogenous targets of C. elegans piRNAs.
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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 | 0.001 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.007 | 0.012 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.057 | 0.031 |
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".