RPL4A
S. cerevisiae
60S ribosomal protein uL4 RPL4A
What the model saw
Gene: RPL4A Organism: Saccharomyces cerevisiae Known functions: 60S ribosomal protein uL4 RPL4A. RNA binding. structural constituent of ribosome.
View unredacted entry
60S ribosomal protein uL4 RPL4A. RNA binding. structural constituent of ribosome.
Solver output
RPL4A encodes a core structural component of the 60S ribosomal large subunit (uL4), directly contributing to ribosome biogenesis and translational capacity. In yeast, ribosome biogenesis is a major downstream effector of the TOR (Target of Rapamycin) nutrient-sensing pathway; high ribosomal activity is associated with pro-growth, pro-aging signaling. Deletion of large ribosomal subunit components, including RPL genes, is well-documented to extend chronological and replicative lifespan in S. cerevisiae, likely by mimicking TOR inhibition and reducing global translation rates. Reduced translation slows the accumulation of misfolded proteins and dampens anabolic signaling, both of which are associated with longevity. Thus, the normal (active) function of RPL4A — promoting ribosome assembly and high translational output — 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 RPL4A. The mechanistic reasoning is sound and well-articulated: RPL4A is a core 60S ribosomal subunit component, and deletion of RPL genes in yeast is well-documented to extend lifespan by reducing translational output and mimicking TOR inhibition. The model correctly identifies the TOR/ribosome biogenesis axis as the key pathway. The confidence of 0.72 is appropriate given the general knowledge about RPL gene deletions extending yeast lifespan. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though "translational regulation" might be more precise — however, the narrative reasoning correctly ties it to TOR signaling, making this acceptable.
Raw API responses
solver
{
"reasoning": "RPL4A encodes a core structural component of the 60S ribosomal large subunit (uL4), directly contributing to ribosome biogenesis and translational capacity. In yeast, ribosome biogenesis is a major downstream effector of the TOR (Target of Rapamycin) nutrient-sensing pathway; high ribosomal activity is associated with pro-growth, pro-aging signaling. Deletion of large ribosomal subunit components, including RPL genes, is well-documented to extend chronological and replicative lifespan in S. cerevisiae, likely by mimicking TOR inhibition and reducing global translation rates. Reduced translation slows the accumulation of misfolded proteins and dampens anabolic signaling, both of which are associated with longevity. Thus, the normal (active) function of RPL4A — promoting ribosome assembly and high translational output — opposes longevity.",
"confidence": 0.72,
"key_pathways": [
"TOR signaling / ribosome biogenesis",
"60S ribosomal large subunit assembly",
"global translational regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPL4A. The mechanistic reasoning is sound and well-articulated: RPL4A is a core 60S ribosomal subunit component, and deletion of RPL genes in yeast is well-documented to extend lifespan by reducing translational output and mimicking TOR inhibition. The model correctly identifies the TOR/ribosome biogenesis axis as the key pathway. The confidence of 0.72 is appropriate given the general knowledge about RPL gene deletions extending yeast lifespan. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though \"translational regulation\" might be more precise — however, the narrative reasoning correctly ties it to TOR signaling, making this acceptable.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}