Transfer <scp>RNA</scp> and small molecule therapeutics for aminoacyl‐<scp>tRNA</scp> synthetase diseases
Bibliographic record
Abstract
Aminoacyl-tRNA synthetases catalyze the ligation of a specific amino acid to its cognate tRNA. The resulting aminoacyl-tRNAs are indispensable intermediates in protein biosynthesis, facilitating the precise decoding of the genetic code. Pathogenic alleles in the aminoacyl-tRNA synthetases can lead to several dominant and recessive disorders. To date, disease-specific treatments for these conditions are largely unavailable. We review pathogenic human synthetase alleles, the molecular and cellular mechanisms of tRNA synthetase diseases, and emerging approaches to allele-specific treatments, including small molecules and nucleic acid-based therapeutics. Current treatment approaches to rescue defective or dysfunctional tRNA synthetase mutants include supplementation with cognate amino acids and delivery of cognate tRNAs to alleviate bottlenecks in translation. Complementary approaches use inhibitors to target the integrated stress response, which can be dysregulated in tRNA synthetase diseases.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.005 |
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".