qars-1
C. elegans
glutamine--tRNA ligase;putative glutamine--tRNA ligase
What the model saw
Gene: qars-1 Organism: Caenorhabditis elegans Known functions: glutamine--tRNA ligase;putative glutamine--tRNA ligase. ATP binding. aminoacyl-tRNA ligase activity. glutamine-tRNA ligase activity. nucleotide binding.
View unredacted entry
glutamine--tRNA ligase;putative glutamine--tRNA ligase. ATP binding. aminoacyl-tRNA ligase activity. glutamine-tRNA ligase activity. nucleotide binding.
Solver output
qars-1 encodes glutaminyl-tRNA synthetase (GlnRS), which catalyzes the ATP-dependent aminoacylation of tRNA^Gln with glutamine, a critical step in translational elongation. Accurate and efficient aminoacyl-tRNA charging is essential for maintaining translational fidelity and proteostasis; defects in this enzyme lead to misincorporation of amino acids, ribosome stalling, and accumulation of misfolded proteins. In C. elegans, proper proteostasis is a well-established pro-longevity mechanism, and aminoacyl-tRNA synthetases are required for normal protein synthesis quality control. Additionally, GlnRS activity connects to the integrated stress response (ISR) via uncharged tRNA sensing through GCN2, where loss of charging capacity can trigger stress signaling that, if chronic, is detrimental. The normal function of qars-1 thus supports proteostasis and translational accuracy, placing it in the pro-longevity category.
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 reasoned that qars-1 (glutaminyl-tRNA synthetase) supports proteostasis and translational fidelity, making it pro-longevity. However, the ground truth indicates it is anti_longevity, meaning that qars-1 activity actually limits lifespan (i.e., reducing its activity extends lifespan). This is consistent with findings in C. elegans where reduced translation/protein synthesis — including through knockdown of aminoacyl-tRNA synthetases — can extend lifespan by reducing overall translation rates, activating stress responses, or mimicking dietary restriction. The model's reasoning about proteostasis support is plausible in isolation but misses the key finding that reduced translation (via qars-1 knockdown) extends lifespan, making qars-1 anti-longevity. The model was moderately confident (0.72) in the wrong direction.
Raw API responses
solver
{
"reasoning": "qars-1 encodes glutaminyl-tRNA synthetase (GlnRS), which catalyzes the ATP-dependent aminoacylation of tRNA^Gln with glutamine, a critical step in translational elongation. Accurate and efficient aminoacyl-tRNA charging is essential for maintaining translational fidelity and proteostasis; defects in this enzyme lead to misincorporation of amino acids, ribosome stalling, and accumulation of misfolded proteins. In C. elegans, proper proteostasis is a well-established pro-longevity mechanism, and aminoacyl-tRNA synthetases are required for normal protein synthesis quality control. Additionally, GlnRS activity connects to the integrated stress response (ISR) via uncharged tRNA sensing through GCN2, where loss of charging capacity can trigger stress signaling that, if chronic, is detrimental. The normal function of qars-1 thus supports proteostasis and translational accuracy, placing it in the pro-longevity category.",
"confidence": 0.72,
"key_pathways": [
"aminoacyl-tRNA biosynthesis",
"translational fidelity and proteostasis",
"integrated stress response / GCN2 signaling"
],
"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 reasoned that qars-1 (glutaminyl-tRNA synthetase) supports proteostasis and translational fidelity, making it pro-longevity. However, the ground truth indicates it is anti_longevity, meaning that qars-1 activity actually limits lifespan (i.e., reducing its activity extends lifespan). This is consistent with findings in C. elegans where reduced translation/protein synthesis — including through knockdown of aminoacyl-tRNA synthetases — can extend lifespan by reducing overall translation rates, activating stress responses, or mimicking dietary restriction. The model's reasoning about proteostasis support is plausible in isolation but misses the key finding that reduced translation (via qars-1 knockdown) extends lifespan, making qars-1 anti-longevity. The model was moderately confident (0.72) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}