RPL12A
S. cerevisiae
60S ribosomal protein uL11 RPL12A
What the model saw
Gene: RPL12A Organism: Saccharomyces cerevisiae Known functions: 60S ribosomal protein uL11 RPL12A. large ribosomal subunit rRNA binding. structural constituent of ribosome.
View unredacted entry
60S ribosomal protein uL11 RPL12A. large ribosomal subunit rRNA binding. structural constituent of ribosome.
Solver output
RPL12A encodes the 60S large ribosomal subunit protein uL11, which is a structural constituent of the ribosome that binds rRNA. Ribosomal protein genes in yeast are well-established modulators of longevity through the TOR (Target of Rapamycin) nutrient-sensing pathway: reduced ribosome biogenesis and translation capacity downstream of TOR inhibition is a conserved pro-longevity intervention. Deletion of many large ribosomal subunit proteins, including components of the 60S subunit, extends chronological and replicative lifespan in S. cerevisiae by mimicking reduced TOR signaling and decreasing global translational output. The uL11/RPL12 protein specifically sits at the ribosomal stalk base and is critical for peptidyl transferase activity and translational fidelity; its normal function sustains high translational rates that are associated with accelerated aging. Thus, the normal (wild-type) function of RPL12A promotes ribosome activity and translation, which opposes longevity.
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 RPL12A. The mechanistic reasoning is sound: ribosomal protein genes in yeast are well-known anti-longevity genes because their deletion extends lifespan by reducing translational output, mimicking TOR inhibition. The model correctly identifies the TOR/nutrient-sensing pathway and ribosome biogenesis as key mechanisms. The specific detail about uL11 sitting at the "ribosomal stalk base" is slightly imprecise (uL11 is at the intersubunit interface/peptidyl transferase center region, not strictly the stalk base), but this is a minor inaccuracy that doesn't undermine the overall mechanistic logic. Confidence of 0.72 is appropriate given the well-established literature on ribosomal protein deletions extending yeast lifespan.
Raw API responses
solver
{
"reasoning": "RPL12A encodes the 60S large ribosomal subunit protein uL11, which is a structural constituent of the ribosome that binds rRNA. Ribosomal protein genes in yeast are well-established modulators of longevity through the TOR (Target of Rapamycin) nutrient-sensing pathway: reduced ribosome biogenesis and translation capacity downstream of TOR inhibition is a conserved pro-longevity intervention. Deletion of many large ribosomal subunit proteins, including components of the 60S subunit, extends chronological and replicative lifespan in S. cerevisiae by mimicking reduced TOR signaling and decreasing global translational output. The uL11/RPL12 protein specifically sits at the ribosomal stalk base and is critical for peptidyl transferase activity and translational fidelity; its normal function sustains high translational rates that are associated with accelerated aging. Thus, the normal (wild-type) function of RPL12A promotes ribosome activity and translation, which opposes longevity.",
"confidence": 0.72,
"key_pathways": [
"TOR signaling / ribosome biogenesis",
"60S ribosomal subunit assembly and translation",
"nutrient-sensing translational regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPL12A. The mechanistic reasoning is sound: ribosomal protein genes in yeast are well-known anti-longevity genes because their deletion extends lifespan by reducing translational output, mimicking TOR inhibition. The model correctly identifies the TOR/nutrient-sensing pathway and ribosome biogenesis as key mechanisms. The specific detail about uL11 sitting at the \"ribosomal stalk base\" is slightly imprecise (uL11 is at the intersubunit interface/peptidyl transferase center region, not strictly the stalk base), but this is a minor inaccuracy that doesn't undermine the overall mechanistic logic. Confidence of 0.72 is appropriate given the well-established literature on ribosomal protein deletions extending yeast lifespan.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}