rrp-8
C. elegans
Ribosomal RNA-processing protein 8
What the model saw
Gene: rrp-8 Organism: Caenorhabditis elegans Known functions: Ribosomal RNA-processing protein 8. methyltransferase activity. rRNA (adenine-N1-)-methyltransferase activity.
View unredacted entry
Ribosomal RNA-processing protein 8. methyltransferase activity. rRNA (adenine-N1-)-methyltransferase activity.
Solver output
RRP-8 is an rRNA adenine-N1-methyltransferase responsible for m1A modification of 18S rRNA (specifically at position A645 in yeast homologs), a conserved modification critical for ribosome biogenesis and translational fidelity. In C. elegans, reduced ribosome biogenesis and translational output are well-established pro-longevity interventions, often acting through the TOR/TORC1 nutrient-sensing axis. However, RRP-8 has been specifically shown in C. elegans to be required for lifespan extension under dietary restriction conditions, placing it as a positive effector of longevity rather than a simple ribosome component whose loss extends life. Loss of rrp-8 suppresses dietary-restriction-induced longevity, indicating its normal function is necessary for the pro-longevity response to nutrient limitation. This connects rRNA methylation and ribosome quality to the deregulated nutrient-sensing hallmark of aging via the DR/TOR pathway.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is internally coherent but leads to the wrong conclusion. The model correctly identifies that rrp-8 loss suppresses dietary-restriction-induced longevity, which would make it anti_longevity (its normal function promotes longevity under DR). However, the model then incorrectly classifies this as pro_longevity, confusing the direction. If loss of rrp-8 suppresses DR-induced lifespan extension, then rrp-8 itself is pro_longevity under DR conditions — but the GenAge classification is anti_longevity, suggesting that rrp-8's normal function actually shortens lifespan (i.e., its loss extends life). The model's mechanistic reasoning about DR and TOR pathway is plausible but the final classification contradicts the ground truth. The model showed moderate confidence (0.62) but still got the direction wrong.
Raw API responses
solver
{
"reasoning": "RRP-8 is an rRNA adenine-N1-methyltransferase responsible for m1A modification of 18S rRNA (specifically at position A645 in yeast homologs), a conserved modification critical for ribosome biogenesis and translational fidelity. In C. elegans, reduced ribosome biogenesis and translational output are well-established pro-longevity interventions, often acting through the TOR/TORC1 nutrient-sensing axis. However, RRP-8 has been specifically shown in C. elegans to be required for lifespan extension under dietary restriction conditions, placing it as a positive effector of longevity rather than a simple ribosome component whose loss extends life. Loss of rrp-8 suppresses dietary-restriction-induced longevity, indicating its normal function is necessary for the pro-longevity response to nutrient limitation. This connects rRNA methylation and ribosome quality to the deregulated nutrient-sensing hallmark of aging via the DR/TOR pathway.",
"confidence": 0.62,
"key_pathways": [
"rRNA N1-adenosine methylation (m1A modification of 18S rRNA)",
"dietary restriction / TOR nutrient-sensing pathway",
"ribosome biogenesis and translational fidelity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is internally coherent but leads to the wrong conclusion. The model correctly identifies that rrp-8 loss suppresses dietary-restriction-induced longevity, which would make it anti_longevity (its normal function promotes longevity under DR). However, the model then incorrectly classifies this as pro_longevity, confusing the direction. If loss of rrp-8 suppresses DR-induced lifespan extension, then rrp-8 itself is pro_longevity under DR conditions — but the GenAge classification is anti_longevity, suggesting that rrp-8's normal function actually shortens lifespan (i.e., its loss extends life). The model's mechanistic reasoning about DR and TOR pathway is plausible but the final classification contradicts the ground truth. The model showed moderate confidence (0.62) but still got the direction wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}