MSK1
S. cerevisiae
lysine--tRNA ligase MSK1
What the model saw
Gene: MSK1 Organism: Saccharomyces cerevisiae Known functions: lysine--tRNA ligase MSK1. ATP binding. aminoacyl-tRNA ligase activity. lysine-tRNA ligase activity. nucleotide binding. tRNA binding.
View unredacted entry
lysine--tRNA ligase MSK1. ATP binding. aminoacyl-tRNA ligase activity. lysine-tRNA ligase activity. nucleotide binding. tRNA binding.
Solver output
MSK1 encodes the mitochondrial lysine-tRNA ligase (LysRS) in S. cerevisiae, responsible for charging tRNA-Lys with lysine in the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Loss or impairment of MSK1 function leads to mitochondrial translational errors, respiratory deficiency, and mitochondrial dysfunction — a recognized hallmark of aging. Maintaining proper mitochondrial proteostasis through accurate tRNA charging supports mitochondrial integrity and energy production, which are strongly associated with longevity in yeast. Therefore, the normal function of MSK1 is expected to be pro-longevity by preserving mitochondrial translation fidelity and respiratory competence.
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 but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — MSK1 is indeed a mitochondrial lysine-tRNA ligase, and the model correctly identifies its role in mitochondrial translation fidelity. However, the model assumed that maintaining mitochondrial function is always pro-longevity, which is not necessarily the case. In yeast, mitochondrial dysfunction can sometimes extend lifespan (e.g., through retrograde signaling or reduced TOR activity). The anti_longevity classification suggests that MSK1 activity actually shortens lifespan, possibly because its deletion or loss leads to beneficial mitochondrial stress responses or reduced OXPHOS that extends lifespan. The model's mechanistic reasoning is directionally incorrect — it assumed loss of function = bad for longevity, when the opposite is true. The confidence of 0.62 is moderate but still wrong. The mechanism class of "loss_of_proteostasis" is also not well-supported for an aminoacyl-tRNA ligase in this context.
Raw API responses
solver
{
"reasoning": "MSK1 encodes the mitochondrial lysine-tRNA ligase (LysRS) in S. cerevisiae, responsible for charging tRNA-Lys with lysine in the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Loss or impairment of MSK1 function leads to mitochondrial translational errors, respiratory deficiency, and mitochondrial dysfunction — a recognized hallmark of aging. Maintaining proper mitochondrial proteostasis through accurate tRNA charging supports mitochondrial integrity and energy production, which are strongly associated with longevity in yeast. Therefore, the normal function of MSK1 is expected to be pro-longevity by preserving mitochondrial translation fidelity and respiratory competence.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation",
"aminoacyl-tRNA biosynthesis",
"oxidative phosphorylation"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface — MSK1 is indeed a mitochondrial lysine-tRNA ligase, and the model correctly identifies its role in mitochondrial translation fidelity. However, the model assumed that maintaining mitochondrial function is always pro-longevity, which is not necessarily the case. In yeast, mitochondrial dysfunction can sometimes extend lifespan (e.g., through retrograde signaling or reduced TOR activity). The anti_longevity classification suggests that MSK1 activity actually shortens lifespan, possibly because its deletion or loss leads to beneficial mitochondrial stress responses or reduced OXPHOS that extends lifespan. The model's mechanistic reasoning is directionally incorrect — it assumed loss of function = bad for longevity, when the opposite is true. The confidence of 0.62 is moderate but still wrong. The mechanism class of \"loss_of_proteostasis\" is also not well-supported for an aminoacyl-tRNA ligase in this context.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}