MSW1
S. cerevisiae
tryptophan--tRNA ligase MSW1
What the model saw
Gene: MSW1 Organism: Saccharomyces cerevisiae Known functions: tryptophan--tRNA ligase MSW1. ATP binding. aminoacyl-tRNA ligase activity. nucleotide binding. tryptophan-tRNA ligase activity.
View unredacted entry
tryptophan--tRNA ligase MSW1. ATP binding. aminoacyl-tRNA ligase activity. nucleotide binding. tryptophan-tRNA ligase activity.
Solver output
MSW1 encodes the mitochondrial tryptophan-tRNA ligase (tryptophanyl-tRNA synthetase) in S. cerevisiae, responsible for charging tRNA-Trp with tryptophan in the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the 8 mitochondrially-encoded proteins, all of which are core subunits of the oxidative phosphorylation complexes. Loss of MSW1 function would impair mitochondrial translation fidelity, leading to proteostatic stress and mitochondrial dysfunction. Proper mitochondrial proteostasis and OXPHOS function are well-established pro-longevity factors in yeast. Additionally, aminoacyl-tRNA synthetases are central to the integrated stress response (ISR) and translational quality control; their normal activity supports proteome integrity. Thus, the normal function of MSW1 promotes longevity by maintaining mitochondrial translational fidelity and proteostasis.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning that MSW1 maintains mitochondrial translational fidelity and proteostasis, and therefore promotes longevity, is logically coherent but leads to the wrong conclusion. The ground truth indicates MSW1 is anti-longevity, meaning its deletion or loss likely extends lifespan. This is consistent with findings that loss of mitochondrial tRNA synthetases can trigger mitochondrial stress responses (like the mitochondrial unfolded protein response, UPRmt) that paradoxically extend lifespan - a phenomenon seen in multiple organisms. The model's reasoning about proteostasis maintenance being pro-longevity is a reasonable prior but misses the nuance that mitochondrial dysfunction can activate compensatory longevity pathways. The model was confidently wrong in both the direction of effect and the mechanistic interpretation.
Raw API responses
solver
{
"reasoning": "MSW1 encodes the mitochondrial tryptophan-tRNA ligase (tryptophanyl-tRNA synthetase) in S. cerevisiae, responsible for charging tRNA-Trp with tryptophan in the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the 8 mitochondrially-encoded proteins, all of which are core subunits of the oxidative phosphorylation complexes. Loss of MSW1 function would impair mitochondrial translation fidelity, leading to proteostatic stress and mitochondrial dysfunction. Proper mitochondrial proteostasis and OXPHOS function are well-established pro-longevity factors in yeast. Additionally, aminoacyl-tRNA synthetases are central to the integrated stress response (ISR) and translational quality control; their normal activity supports proteome integrity. Thus, the normal function of MSW1 promotes longevity by maintaining mitochondrial translational fidelity and proteostasis.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial translation and tRNA aminoacylation",
"oxidative phosphorylation complex assembly",
"mitochondrial proteostasis"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. The model's reasoning that MSW1 maintains mitochondrial translational fidelity and proteostasis, and therefore promotes longevity, is logically coherent but leads to the wrong conclusion. The ground truth indicates MSW1 is anti-longevity, meaning its deletion or loss likely extends lifespan. This is consistent with findings that loss of mitochondrial tRNA synthetases can trigger mitochondrial stress responses (like the mitochondrial unfolded protein response, UPRmt) that paradoxically extend lifespan - a phenomenon seen in multiple organisms. The model's reasoning about proteostasis maintenance being pro-longevity is a reasonable prior but misses the nuance that mitochondrial dysfunction can activate compensatory longevity pathways. The model was confidently wrong in both the direction of effect and the mechanistic interpretation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}