yars-2
C. elegans
Tyrosine--tRNA ligase
What the model saw
Gene: yars-2 Organism: Caenorhabditis elegans Known functions: Tyrosine--tRNA ligase. ATP binding. RNA binding. aminoacyl-tRNA ligase activity. nucleotide binding. tyrosine-tRNA ligase activity.
View unredacted entry
Tyrosine--tRNA ligase. ATP binding. RNA binding. aminoacyl-tRNA ligase activity. nucleotide binding. tyrosine-tRNA ligase activity.
Solver output
yars-2 encodes a mitochondrial tyrosine-tRNA ligase (aminoacyl-tRNA synthetase), which charges tRNA-Tyr with tyrosine to support mitochondrial translation. Robust mitochondrial translation sustains oxidative phosphorylation complex assembly, which in turn drives high mTORC1/TOR signaling activity — a key nutrient-sensing axis whose attenuation is well-established to extend lifespan in C. elegans. Partial loss-of-function of mitochondrial aminoacyl-tRNA synthetases (including related enzymes like lars-2, mars-2) in C. elegans triggers the mitochondrial unfolded protein response (UPRmt) and reduces mitochondrial translation, which paradoxically extends lifespan through retrograde signaling. Therefore, the normal (wild-type) function of yars-2 — promoting full mitochondrial translational capacity — opposes this longevity-extending pathway, making it anti-longevity in its normal role. This places yars-2 in the nutrient-sensing/TOR axis as well as mitochondrial function, but the primary mechanistic link to lifespan is through mitochondrial translation supporting anabolic/TOR signaling.
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 correctly predicts anti_longevity for yars-2. However, the mechanistic reasoning is questionable. The model classifies the mechanism as "deregulated_nutrient_sensing" and draws a speculative link between mitochondrial translation → OXPHOS → mTORC1/TOR signaling. While the core logic (mitochondrial aminoacyl-tRNA synthetase knockdown extends lifespan via UPRmt, so wild-type function is anti-longevity) is directionally reasonable, the primary mechanism for mitochondrial aminoacyl-tRNA synthetases in C. elegans longevity is through mitochondrial function/UPRmt, not TOR/nutrient sensing. The TOR connection is a stretch and not well-supported. The model correctly identifies the UPRmt pathway but then incorrectly emphasizes TOR/mTORC1 as the primary mechanistic link. The reasoning is partially correct but the mechanism classification is wrong.
Raw API responses
solver
{
"reasoning": "yars-2 encodes a mitochondrial tyrosine-tRNA ligase (aminoacyl-tRNA synthetase), which charges tRNA-Tyr with tyrosine to support mitochondrial translation. Robust mitochondrial translation sustains oxidative phosphorylation complex assembly, which in turn drives high mTORC1/TOR signaling activity — a key nutrient-sensing axis whose attenuation is well-established to extend lifespan in C. elegans. Partial loss-of-function of mitochondrial aminoacyl-tRNA synthetases (including related enzymes like lars-2, mars-2) in C. elegans triggers the mitochondrial unfolded protein response (UPRmt) and reduces mitochondrial translation, which paradoxically extends lifespan through retrograde signaling. Therefore, the normal (wild-type) function of yars-2 — promoting full mitochondrial translational capacity — opposes this longevity-extending pathway, making it anti-longevity in its normal role. This places yars-2 in the nutrient-sensing/TOR axis as well as mitochondrial function, but the primary mechanistic link to lifespan is through mitochondrial translation supporting anabolic/TOR signaling.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation / UPRmt",
"TOR/mTORC1 nutrient sensing",
"aminoacyl-tRNA biosynthesis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicts anti_longevity for yars-2. However, the mechanistic reasoning is questionable. The model classifies the mechanism as \"deregulated_nutrient_sensing\" and draws a speculative link between mitochondrial translation → OXPHOS → mTORC1/TOR signaling. While the core logic (mitochondrial aminoacyl-tRNA synthetase knockdown extends lifespan via UPRmt, so wild-type function is anti-longevity) is directionally reasonable, the primary mechanism for mitochondrial aminoacyl-tRNA synthetases in C. elegans longevity is through mitochondrial function/UPRmt, not TOR/nutrient sensing. The TOR connection is a stretch and not well-supported. The model correctly identifies the UPRmt pathway but then incorrectly emphasizes TOR/mTORC1 as the primary mechanistic link. The reasoning is partially correct but the mechanism classification is wrong.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}