AMPK modulates a DEAH Box RNA-helicase to attenuate TOR signaling and establish developmental quiescence
Bibliographic record
Abstract
Abstract Developmental plasticity allows organisms to adapt to environmental stress and improve reproductive fitness. Caenorhabditis elegans adapts to starvation and other stressors by transiting through an alternate developmental stage called dauer, which allows them to remain quiescent for several months, and yet fully retain reproductive fitness when they resume development. The AMP-activated protein kinase (AMPK) is essential for this plasticity as its compromise leads to germline hyperplasia during the dauer stage, dramatically reducing post-dauer fertility upon recovery from this stage, while also shortening survival. We identified a putative RNA-binding helicase (HZL-1) that is targeted by AMPK, the compromise of which suppresses several AMPK mutant phenotypes. HZL-1 shares significant similarity with the conserved HELZ family of RNA helicases, possessing characteristic DEAH helicase motifs, a predicted ATP binding motif, and three intrinsically disordered regions that are crucial for its localization and function. Curiously, HZL-1 is expressed and exerts its function in the intestine, yet its elimination suppresses the aberrant germ cell proliferation, while restoring germline quiescence and subsequent post-dauer fertility. CLIP-seq data revealed that HZL-1 binds several mRNAs during the dauer stage, resulting in a pronounced germline hyperplasia in the dauer germ line of AMPK mutants. Among these, the most enriched RNA bound to HZL-1, argk-1 , is required for fertility in HZL-1 mutants, and functions by suppressing TOR activity in the germ line of AMPK dauer larvae, thereby preserving germline quiescence. These findings underscore the intricate role of RNAs and RNA-binding helicases in the complex interplay of genetic signals that animals have acquired to ensure their effective transit through periods of environmental challenge.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".