RPS18A
S. cerevisiae
40S ribosomal protein uS13 RPS18A
What the model saw
Gene: RPS18A Organism: Saccharomyces cerevisiae Known functions: 40S ribosomal protein uS13 RPS18A. RNA binding. nucleic acid binding. structural constituent of ribosome.
View unredacted entry
40S ribosomal protein uS13 RPS18A. RNA binding. nucleic acid binding. structural constituent of ribosome.
Solver output
RPS18A encodes the 40S ribosomal small subunit protein uS13, a structural constituent of the ribosome. Ribosomal protein genes in yeast are well-established regulators of longevity through the TOR (Target of Rapamycin) signaling axis: high ribosome biogenesis and translational activity downstream of TORC1 promotes growth but shortens lifespan. Deletion of many small ribosomal subunit proteins, including components of the 40S subunit, extends both replicative and chronological lifespan in S. cerevisiae, consistent with reduced translational capacity mimicking dietary restriction or TORC1 inhibition. The uS13/RPS18 protein sits at the mRNA entry channel of the 40S subunit and is essential for translation initiation and elongation fidelity, meaning its normal function sustains high translational output that is pro-growth but anti-longevity. This places RPS18A squarely in the nutrient-sensing/TOR pathway where ribosome activity is the key effector node opposing lifespan extension.
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 predicted anti_longevity for RPS18A. The mechanistic reasoning is sound and well-grounded: ribosomal protein genes in yeast are well-known anti-longevity factors, as their deletion typically extends lifespan via reduced translational output mimicking TOR inhibition/dietary restriction. The model correctly identifies the TOR-ribosome biogenesis axis as the key pathway. The mechanism_class of "deregulated_nutrient_sensing" is a reasonable categorization, though "translation/ribosome biogenesis" might be more precise. The confidence of 0.72 is appropriate given the general pattern of ribosomal protein deletions extending lifespan in yeast. Overall, this is a well-reasoned and correct prediction.
Raw API responses
solver
{
"reasoning": "RPS18A encodes the 40S ribosomal small subunit protein uS13, a structural constituent of the ribosome. Ribosomal protein genes in yeast are well-established regulators of longevity through the TOR (Target of Rapamycin) signaling axis: high ribosome biogenesis and translational activity downstream of TORC1 promotes growth but shortens lifespan. Deletion of many small ribosomal subunit proteins, including components of the 40S subunit, extends both replicative and chronological lifespan in S. cerevisiae, consistent with reduced translational capacity mimicking dietary restriction or TORC1 inhibition. The uS13/RPS18 protein sits at the mRNA entry channel of the 40S subunit and is essential for translation initiation and elongation fidelity, meaning its normal function sustains high translational output that is pro-growth but anti-longevity. This places RPS18A squarely in the nutrient-sensing/TOR pathway where ribosome activity is the key effector node opposing lifespan extension.",
"confidence": 0.72,
"key_pathways": [
"TORC1-ribosome biogenesis axis",
"40S ribosomal translation initiation",
"dietary restriction / nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPS18A. The mechanistic reasoning is sound and well-grounded: ribosomal protein genes in yeast are well-known anti-longevity factors, as their deletion typically extends lifespan via reduced translational output mimicking TOR inhibition/dietary restriction. The model correctly identifies the TOR-ribosome biogenesis axis as the key pathway. The mechanism_class of \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"translation/ribosome biogenesis\" might be more precise. The confidence of 0.72 is appropriate given the general pattern of ribosomal protein deletions extending lifespan in yeast. Overall, this is a well-reasoned and correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}