A NETWORK OF PROTEIN COMPLEXES SIGNALING TO THE RNA POLYMERASE II TRANSCRIPTION APPARATUS IN HUMAN CELLS
Bibliographic record
Abstract
The enzyme RNA polymerase (RNAP) II, whose activity is modulated by many regulatory proteins, synthesizes all mRNA in eukaryotes. To explore the network of protein complexes that signal to RNAP II in mammalian cells, we have developed a systematic procedure where the expression of affinity tagged polypeptides and the purification of their associated proteins, as they prospectively exist in vivo, is coupled to protein identification by mass spectrometry (MS). All newly detected interactions were validated experimentally and novel interaction partners were reciprocally tagged, purified and the eluates characterized by MS. Thirty tagged polypeptides yield a network of more than 325 validated interactions. Our results identify nine previously uncharacterized proteins to which we have inferred a function on the basis of their network connections, bioinformatics and the effect of silencing their homologues on global gene expression in yeast. These polypeptides participate in defining at least two novel interfaces linking RNAP II to specific regulatory machineries, one involved in alternative pre‐mRNA splicing and arginine methylation and the other, comprised of chaperone/scaffolding‐related factors, linking RNAP II to the Mediator, the Integrator and chromatin‐remodeling factors. Together, our results define novel transcriptional regulators, pathways and mechanisms.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".