Differential effect of ubiquitous and germline depletion of Integrator complex function on <i>C. elegans</i> physiology
Why this work is in the frame
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Bibliographic record
Abstract
The Integrator is a metazoan-conserved protein complex with endonuclease activity that functions to cleave various RNA substrates to shape transcriptome homeostasis by coordinating small nuclear RNA biogenesis to premature transcription termination. Depletion of Integrator results in developmental defects across different model systems and has emerged as a causative factor in human neurodevelopmental syndromes. Here, we used the model system Caenorhabditis elegans to enable study of the temporal effects of Integrator depletion on various physiological parameters with the auxin-inducible degron system that permitted depletion of INTS-4 (Integrator subunit) catalytic subunit of the protein complex. We found that Integrator activity is critical and required for C. elegans development within the L1 larval stage but becomes dispensable for development and lifespan after the animals have reached the L2/L3 stage. Depletion of INTS-4 only shortened lifespan if auxin was introduced at the L1 stage, suggesting that the previously described lifespan reduction by Integrator inhibition is linked to developmental growth defects. We also found that while germline-specific degradation of Integrator results in the accumulation of misprocessed snRNA transcript, it did not impair the development or lifespan but surprisingly increased progeny production. Together, our study illustrates a temporal, and a potentially tissue-specific requirement of the Integrator complex function in shaping whole organism development, aging, and reproduction.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it