Codon usage and amino acid identity are major determinants of mRNA stability in humans
Bibliographic record
Abstract
mRNA degradation is a critical, yet poorly understood, aspect of gene expression. Previous studies demonstrate that codon content acts as a major determinant of mRNA stability in model organisms. In humans, the importance of open reading frame (ORF)-mediated regulation remains unclear. Here, we globally analyzed mRNA stability for both endogenous and human ORFeome collection mRNAs in human cells. Consistent with previous studies, we observed that synonymous codon usage impacts human mRNA decay. Unexpectedly, amino acid identity also acts as a driver of translation-dependent decay, meaning that primary protein sequence dictates overall mRNA levels and, consequently, protein abundance. Both codon usage and amino acid identity affect translational elongation rate to varying degrees in distinct organisms, with the net result being sensed by mRNA degradation machinery. In humans, interplay between ORF- and UTR-mediated control of mRNA stability may be critical to offset this fundamental relationship between protein sequence and mRNA abundance.
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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) | 0.001 | 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 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".