A minor alternative transcript of the fumarylacetoacetate hydrolase gene produces a protein despite being likely subjected to nonsense-mediated mRNA decay
Bibliographic record
Abstract
BACKGROUND: Coupling of alternative splicing with nonsense-mediated mRNA decay (NMD) may regulate gene expression. We report here the identification of a nonsense alternative transcript of the fumarylacetoacetate hydrolase (fah) gene, which produces a protein despite the fact that it is subject to NMD. RESULTS: During the characterization of the effects of the W262X nonsense mutation on FAH mRNA metabolism, two alternative transcripts (del100 and del231) of the fah gene were identified. Del100 lacks exon 8 and as a consequence, the reading frame is shifted and a premature termination codon appears at the 3'end of exon 10. Exons 8 and 9 are skipped in del231, without any disruption of the reading frame. Specific amplification of these transcripts demonstrate that they are produced through minor alternative splicing pathways, and that they are not caused by the W262X mutation per se. As shown with an antiserum raised against the C-terminal part of the putative DEL100 protein, the del100 transcript produces a protein, expressed at different levels in various human tissues. Interestingly, the del100 transcript seems to be subjected to nonsense-mediated mRNA decay, as its level was stabilized following a cycloheximide treatment. CONCLUSIONS: The del100 and del231 transcripts arise due to minor alternative splicing pathways and del100 is likely subjected to nonsense-mediated mRNA decay. However the remaining amount of transcript seems sufficient to produce a protein in different human tissues. This suggests that NMD has a broader role than simply eliminating aberrant transcripts and when coupled to alternative splicing, may act to modulate gene expression, by allowing the production of low amounts of protein.
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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 | 0.001 | 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".