RPL2B
S. cerevisiae
60S ribosomal protein uL2 RPL2B
What the model saw
Gene: RPL2B Organism: Saccharomyces cerevisiae Known functions: 60S ribosomal protein uL2 RPL2B. RNA binding. structural constituent of ribosome.
View unredacted entry
60S ribosomal protein uL2 RPL2B. RNA binding. structural constituent of ribosome.
Solver output
RPL2B encodes a core structural component of the 60S ribosomal large subunit (uL2), directly contributing to ribosome biogenesis and translational capacity. In yeast, reduced ribosomal protein gene dosage — particularly of large subunit components — is well-established to extend chronological and replicative lifespan, largely through attenuation of TORC1-driven protein synthesis. Downregulation of ribosome biogenesis mimics dietary restriction and dampens TOR signaling output, a key pro-longevity intervention. RPL2B's normal function sustains high translational activity, which promotes growth but accelerates aging via nutrient-sensing pathway hyperactivation. Deletion of RPL2B or its paralog RPL2A has been shown to extend replicative lifespan in genome-wide screens, consistent with the broader pattern that ribosomal protein deletions are enriched among longevity-extending mutations in S. cerevisiae.
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 RPL2B. The reasoning is well-grounded: RPL2B is a 60S ribosomal protein, and deletion of ribosomal protein genes in yeast is well-established to extend lifespan, making the wild-type gene anti-longevity. The model correctly identifies the TORC1/ribosome biogenesis axis as the key mechanism, noting that reduced ribosomal protein dosage mimics dietary restriction and attenuates TOR signaling. The mechanism classification as "deregulated_nutrient_sensing" is appropriate given the TOR pathway connection. The model also correctly notes genome-wide screen evidence for RPL2B/RPL2A deletion extending replicative lifespan. Confidence of 0.72 is reasonable and well-calibrated.
Raw API responses
solver
{
"reasoning": "RPL2B encodes a core structural component of the 60S ribosomal large subunit (uL2), directly contributing to ribosome biogenesis and translational capacity. In yeast, reduced ribosomal protein gene dosage — particularly of large subunit components — is well-established to extend chronological and replicative lifespan, largely through attenuation of TORC1-driven protein synthesis. Downregulation of ribosome biogenesis mimics dietary restriction and dampens TOR signaling output, a key pro-longevity intervention. RPL2B's normal function sustains high translational activity, which promotes growth but accelerates aging via nutrient-sensing pathway hyperactivation. Deletion of RPL2B or its paralog RPL2A has been shown to extend replicative lifespan in genome-wide screens, consistent with the broader pattern that ribosomal protein deletions are enriched among longevity-extending mutations in S. cerevisiae.",
"confidence": 0.72,
"key_pathways": [
"TORC1/ribosome biogenesis axis",
"translational regulation",
"ribosomal large subunit assembly"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPL2B. The reasoning is well-grounded: RPL2B is a 60S ribosomal protein, and deletion of ribosomal protein genes in yeast is well-established to extend lifespan, making the wild-type gene anti-longevity. The model correctly identifies the TORC1/ribosome biogenesis axis as the key mechanism, noting that reduced ribosomal protein dosage mimics dietary restriction and attenuates TOR signaling. The mechanism classification as \"deregulated_nutrient_sensing\" is appropriate given the TOR pathway connection. The model also correctly notes genome-wide screen evidence for RPL2B/RPL2A deletion extending replicative lifespan. Confidence of 0.72 is reasonable and well-calibrated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}