A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in <i>C. elegans</i>
Bibliographic record
Abstract
The Caenorhabditis elegans Nuclear Hormone Receptor NHR-49 coordinates expression of fatty acid (FA) metabolic genes during periods of feeding and in response to fasting. Here we report the identification of MDT-15, a subunit of the C. elegans Mediator complex, as an NHR-49-interacting protein and transcriptional coactivator. Knockdown of mdt-15 by RNA interference (RNAi) prevented fasting-induced mRNA accumulation of NHR-49 targets in vivo, and fasting-independent expression of other NHR-49 target genes, including two FA-Delta9-desaturases (fat-5, fat-7). Interestingly, mdt-15 RNAi affected additional FA-metabolism genes (including the third FA-Delta9-desaturase, fat-6) that are regulated independently of NHR-49, suggesting that distinct unidentified regulatory factors also recruit MDT-15 to selectively modulate metabolic gene expression. The deregulation of FA-Delta9-desaturases by knockdown of mdt-15 correlated with dramatically decreased levels of unsaturated FAs and multiple deleterious phenotypes (short life span, sterility, uncoordinated locomotion, and morphological defects). Importantly, dietary addition of specific polyunsaturated FAs partially suppressed these pleiotropic phenotypes. Thus, failure to properly govern FA-Delta9-desaturation contributed to decreased nematode viability. Our findings imply that a single subunit of the Mediator complex, MDT-15, integrates the activities of several distinct regulatory factors to coordinate metabolic and hormonal regulation of FA metabolism.
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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 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".