RPL43B
S. cerevisiae
60S ribosomal protein eL43 RPL43B
What the model saw
Gene: RPL43B Organism: Saccharomyces cerevisiae Known functions: 60S ribosomal protein eL43 RPL43B. structural constituent of ribosome. zinc ion binding.
View unredacted entry
60S ribosomal protein eL43 RPL43B. structural constituent of ribosome. zinc ion binding.
Solver output
RPL43B encodes a structural component of the 60S ribosomal large subunit (eL43), directly contributing to ribosome biogenesis and translational capacity. In yeast, reduced ribosomal protein gene dosage — particularly of 60S subunit components — is well established to extend chronological and replicative lifespan, largely through attenuation of TORC1-driven protein synthesis and downstream effects mimicking dietary restriction. Deletion of many RPL genes activates the retrograde response and reduces global translation rates, which dampens anabolic signaling and promotes longevity. The zinc ion binding activity of eL43 is integral to its structural role within the ribosome rather than a separate regulatory function. Thus, the normal (wild-type) function of RPL43B — supporting full ribosomal assembly and robust translation — opposes longevity by maintaining high translational output downstream of nutrient-sensing pathways.
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 RPL43B. The mechanistic reasoning is sound: ribosomal protein genes (especially 60S subunit components) are well-established anti-longevity factors in yeast, as their deletion extends lifespan by reducing translational output and mimicking dietary restriction via TORC1 pathway attenuation. The model correctly identifies that the wild-type function of RPL43B (supporting ribosome assembly and translation) opposes longevity. The mechanism_class "deregulated_nutrient_sensing" is a reasonable but slightly imprecise label — the more direct mechanism is reduced translation/ribosome biogenesis rather than nutrient sensing per se, though these are closely linked. Overall, the reasoning is well-articulated and mechanistically accurate.
Raw API responses
solver
{
"reasoning": "RPL43B encodes a structural component of the 60S ribosomal large subunit (eL43), directly contributing to ribosome biogenesis and translational capacity. In yeast, reduced ribosomal protein gene dosage — particularly of 60S subunit components — is well established to extend chronological and replicative lifespan, largely through attenuation of TORC1-driven protein synthesis and downstream effects mimicking dietary restriction. Deletion of many RPL genes activates the retrograde response and reduces global translation rates, which dampens anabolic signaling and promotes longevity. The zinc ion binding activity of eL43 is integral to its structural role within the ribosome rather than a separate regulatory function. Thus, the normal (wild-type) function of RPL43B — supporting full ribosomal assembly and robust translation — opposes longevity by maintaining high translational output downstream of nutrient-sensing pathways.",
"confidence": 0.72,
"key_pathways": [
"TORC1-driven ribosome biogenesis",
"60S ribosomal large subunit assembly",
"translational regulation and nutrient sensing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for RPL43B. The mechanistic reasoning is sound: ribosomal protein genes (especially 60S subunit components) are well-established anti-longevity factors in yeast, as their deletion extends lifespan by reducing translational output and mimicking dietary restriction via TORC1 pathway attenuation. The model correctly identifies that the wild-type function of RPL43B (supporting ribosome assembly and translation) opposes longevity. The mechanism_class \"deregulated_nutrient_sensing\" is a reasonable but slightly imprecise label — the more direct mechanism is reduced translation/ribosome biogenesis rather than nutrient sensing per se, though these are closely linked. Overall, the reasoning is well-articulated and mechanistically accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}