rpoa-2
C. elegans
DNA-directed RNA polymerase I subunit RPA2 homolog
What the model saw
Gene: rpoa-2 Organism: Caenorhabditis elegans Known functions: DNA-directed RNA polymerase I subunit RPA2 homolog. 5'-3' RNA polymerase activity. DNA binding. DNA-directed RNA polymerase activity. ribonucleoside binding.
View unredacted entry
DNA-directed RNA polymerase I subunit RPA2 homolog. 5'-3' RNA polymerase activity. DNA binding. DNA-directed RNA polymerase activity. ribonucleoside binding.
Solver output
rpoa-2 encodes a subunit of RNA Polymerase I (Pol I), the enzyme exclusively responsible for transcribing ribosomal RNA (rRNA) precursors. Pol I activity is a major downstream effector of nutrient-sensing pathways, particularly TOR (Target of Rapamycin) signaling, which upregulates rRNA synthesis and ribosome biogenesis in response to nutrient availability. Elevated Pol I activity drives increased ribosome production, which promotes growth and anabolic metabolism but is associated with accelerated aging. In C. elegans, reduction of ribosomal biogenesis components (including rRNA synthesis machinery) has been shown to extend lifespan, consistent with the idea that high Pol I activity is pro-growth but anti-longevity. Thus, the normal function of rpoa-2 — sustaining robust rRNA transcription — opposes longevity by maintaining high ribosome biogenesis downstream of TOR signaling.
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 rpoa-2. The mechanistic reasoning is sound: RNA Pol I drives rRNA transcription and ribosome biogenesis, which is downstream of TOR/nutrient-sensing pathways, and reducing ribosome biogenesis is well-established to extend lifespan in C. elegans. The classification of "deregulated_nutrient_sensing" is a reasonable framing, though "ribosome biogenesis" might be a more direct label. The reasoning is well-articulated and biologically accurate. Confidence of 0.72 is appropriate given the indirect nature of the inference from known functions.
Raw API responses
solver
{
"reasoning": "rpoa-2 encodes a subunit of RNA Polymerase I (Pol I), the enzyme exclusively responsible for transcribing ribosomal RNA (rRNA) precursors. Pol I activity is a major downstream effector of nutrient-sensing pathways, particularly TOR (Target of Rapamycin) signaling, which upregulates rRNA synthesis and ribosome biogenesis in response to nutrient availability. Elevated Pol I activity drives increased ribosome production, which promotes growth and anabolic metabolism but is associated with accelerated aging. In C. elegans, reduction of ribosomal biogenesis components (including rRNA synthesis machinery) has been shown to extend lifespan, consistent with the idea that high Pol I activity is pro-growth but anti-longevity. Thus, the normal function of rpoa-2 — sustaining robust rRNA transcription — opposes longevity by maintaining high ribosome biogenesis downstream of TOR signaling.",
"confidence": 0.72,
"key_pathways": [
"TOR signaling / ribosome biogenesis",
"RNA Polymerase I-mediated rRNA transcription",
"nutrient-sensing growth regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for rpoa-2. The mechanistic reasoning is sound: RNA Pol I drives rRNA transcription and ribosome biogenesis, which is downstream of TOR/nutrient-sensing pathways, and reducing ribosome biogenesis is well-established to extend lifespan in C. elegans. The classification of \"deregulated_nutrient_sensing\" is a reasonable framing, though \"ribosome biogenesis\" might be a more direct label. The reasoning is well-articulated and biologically accurate. Confidence of 0.72 is appropriate given the indirect nature of the inference from known functions.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}