Transcriptional diversity at the UGT2B7 locus is dictated by extensive pre-mRNA splicing mechanisms that give rise to multiple mRNA splice variants
Bibliographic record
Abstract
OBJECTIVE: UGT2B7 is a key member of the UDP-glucuronosyltransferase (UGT) family that participates in glucuronidation of endogenous compounds and pharmaceuticals. Much evidence suggests a large interindividual variability of UGT2B7-mediated glucuronidation, which is still unexplained by polymorphisms. We hypothesized that alternative splicing may be responsible for the variability in the UGT2B7 function. METHODS: We carried out a comprehensive scan for additional exons at this locus and discovered multiple alternative splicing events. We then determined transcript expression profiles across a large variety of human tissues and assessed some of these variants for their glucuronidation activity in human cells. RESULTS: In-depth analysis of the UGT2B7 gene structure led to the discovery of six novel exons. Kidney and liver samples presented the greatest enrichment of tissue-specific splicing, with 21 new UGT2B7 transcripts isolated. Furthermore, transcription from the proximal promoter (exon 1), associated with the active UGT2B7 mRNA isoform 1 (UGT2B7_v1), is most commonly observed in the gastrointestinal tract, whereas a distal promoter (exon 1a) induces the exclusion of the canonical exon 1 and is active in hormone-related tissues. We also showed that novel transcripts with alternative 3' ends could be translated into proteins lacking glucuronosyltransferase activity in human cells but acting as negative regulators on transferase activity when coexpressed with the active UGT2B7 protein. CONCLUSION: Our findings point toward a significant variability in structure, abundance, and tissue-specific UGT2B7 transcriptome, in addition to novel functions for UGT2B7-derived proteins, all of which may ensure the production of tissue-specific proteomes and functions.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".