The ratio of ±KTS splice variants of the Wilms’ tumour suppressor protein WT1 mRNA is determined by an intronic enhancer
Bibliographic record
Abstract
Alternative splicing of the primary transcript of the Wilms' tumour suppressor gene WT1 involving 2 overlapping 5' splice sites at the end of exon 9 results in the insertion of 2 amino acids (KTS) between zinc fingers 3 and 4 of the protein. The presence or absence of these 3 amino acids has consequences for DNA binding affinity, protein-protein interactions, and subnuclear localization. Disruption of the characteristic +KTS to -KTS ratio of mRNA isoforms as a result of mutations in the +KTS splice site results in Frasier syndrome. Mutational analysis of a WT1 minigene construct was carried out to search for sequences that regulate the +/-KTS alternative splicing event. A strong pyrimidine-rich intronic enhancer that increases the use of the +KTS splice site was identified. Cross-linking experiments with nuclear extracts demonstrated that this enhancer specifically binds a protein with a molecular mass of 42+/-2 kDa. One candidate for this trans-factor is the splicing regulator TIA-1, which binds to the pyrimidine-rich enhancer in the primary transcript from the minigene construct and increases the +/-KTS splicing ratio. The observation that TIA-1 and WT1 are both involved in apoptosis supports our proposal for a functional link between these proteins.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".