RPL26A
S. cerevisiae
60S ribosomal protein uL24 RPL26A
What the model saw
Gene: RPL26A Organism: Saccharomyces cerevisiae Known functions: 60S ribosomal protein uL24 RPL26A. RNA binding. structural constituent of ribosome.
View unredacted entry
60S ribosomal protein uL24 RPL26A. RNA binding. structural constituent of ribosome.
Solver output
RPL26A encodes a structural component of the 60S ribosomal large subunit (uL24), 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. Decreased ribosome abundance mimics dietary restriction by dampening anabolic signaling downstream of TOR, reducing global translation rates and associated proteotoxic stress. RPL26A's normal function thus promotes ribosome assembly and high translational output, which is associated with accelerated aging in yeast. Deletion of many RPL genes, including those encoding 60S subunit proteins, is among the most robust pro-longevity interventions in S. cerevisiae screens, placing the wild-type gene in an anti-longevity role.
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 RPL26A. The mechanistic reasoning is sound and well-articulated: RPL26A encodes a 60S ribosomal protein, and deletion of ribosomal protein genes (especially large subunit components) is a well-established pro-longevity intervention in yeast, placing the wild-type gene in an anti-longevity role. The model correctly identifies the TOR/ribosome biogenesis pathway and dietary restriction mimicry as key mechanisms. The mechanism_class of "deregulated_nutrient_sensing" is a reasonable classification, though "translational_regulation" or "ribosome_biogenesis" might be more precise — however, the TOR connection makes this acceptable. Confidence of 0.72 is appropriate given the general knowledge about ribosomal protein deletions extending lifespan in yeast.
Raw API responses
solver
{
"reasoning": "RPL26A encodes a structural component of the 60S ribosomal large subunit (uL24), 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. Decreased ribosome abundance mimics dietary restriction by dampening anabolic signaling downstream of TOR, reducing global translation rates and associated proteotoxic stress. RPL26A's normal function thus promotes ribosome assembly and high translational output, which is associated with accelerated aging in yeast. Deletion of many RPL genes, including those encoding 60S subunit proteins, is among the most robust pro-longevity interventions in S. cerevisiae screens, placing the wild-type gene in an anti-longevity role.",
"confidence": 0.72,
"key_pathways": [
"TORC1/ribosome biogenesis",
"translational regulation",
"dietary restriction mimicry"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPL26A. The mechanistic reasoning is sound and well-articulated: RPL26A encodes a 60S ribosomal protein, and deletion of ribosomal protein genes (especially large subunit components) is a well-established pro-longevity intervention in yeast, placing the wild-type gene in an anti-longevity role. The model correctly identifies the TOR/ribosome biogenesis pathway and dietary restriction mimicry as key mechanisms. The mechanism_class of \"deregulated_nutrient_sensing\" is a reasonable classification, though \"translational_regulation\" or \"ribosome_biogenesis\" might be more precise — however, the TOR connection makes this acceptable. Confidence of 0.72 is appropriate given the general knowledge about ribosomal protein deletions extending lifespan in yeast.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}