The CrkRS/CDK12 kinase is activated by a novel isoform of Cyclin K and phosphorylates the C‐terminal domain of RNA Pol II
Bibliographic record
Abstract
CrkRS (Cdc2‐related kinase, Arg/Ser), or CDK12 (Cyclin Dependent Kinase 12), is a ser/thr kinase believed to coordinate transcription and RNA splicing. While CrkRS complexes were known to phosphorylate the C‐Terminal Domain (CTD) of RNA Pol II, the responsible cyclin was not known. However, others showed that co‐expression of CrkRS and Cyclin L could affect the alternative splicing of a model substrate. Using immunoprecipitation and mass spectrometry (IP‐MS), we identified the protein constituents of endogenous CrkRS complexes. In addition to several spliceosome‐related proteins, we identified a novel 65 kDa isoform of Cyclin K, whereas the known isoform is 43 kDa. We did not observe Cyclin L. Previously, endogenous Cyclin K complexes were known to phosphorylate the CTD, yet the responsible kinase was not identified. Using yeast‐two hybrid and co‐expression experiments others identified CDK9 as a Cyclin K partner and that CDK9/Cyclin K could regulate transcription. Using IP‐MS, we show that Cyclin K complexes isolated from mammalian cells contain CrkRS but do not contain CDK9, and that CDK9 complexes contain Cyclin T1 and not Cyclin K, within detection limits. The co‐expression of CrkRS with either isoform of Cyclin K showed increased CTD kinase activity compared to controls. Our data suggest the primary cyclin partner for CrkRS is Cyclin K and that Cyclin K is sufficient to activate CrkRS to phosphorylate the CTD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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".