let-611
C. elegans
DNA-directed RNA polymerase III subunit RPC3
What the model saw
Gene: let-611 Organism: Caenorhabditis elegans Known functions: DNA-directed RNA polymerase III subunit RPC3. DNA binding. single-stranded DNA binding.
View unredacted entry
DNA-directed RNA polymerase III subunit RPC3. DNA binding. single-stranded DNA binding.
Solver output
let-611 encodes the RPC3 subunit of RNA Polymerase III (Pol III), which is the catalytic core subunit responsible for transcribing small non-coding RNAs including tRNAs, 5S rRNA, and other structural RNAs. Pol III activity is a major anabolic output directly regulated by nutrient-sensing pathways such as TOR (TORC1), and elevated Pol III activity drives ribosome biogenesis and translational capacity. In multiple model organisms including C. elegans, yeast, and Drosophila, reduction of Pol III activity (via subunit knockdown or maf1 overexpression, a Pol III repressor) extends lifespan, while high Pol III activity is associated with shortened lifespan. The normal pro-growth function of RPC3/let-611 thus promotes anabolic signaling that opposes longevity. Its DNA-binding and ssDNA-binding activities are consistent with its role in promoter recognition and transcription initiation at Pol III-dependent genes, reinforcing its role in driving tRNA and ribosomal RNA synthesis downstream of TOR.
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 let-611 (RNA Pol III subunit RPC3). The mechanistic reasoning is excellent: it correctly identifies that Pol III activity drives tRNA/rRNA synthesis downstream of TOR/TORC1, and that reduction of Pol III activity extends lifespan in multiple organisms including C. elegans. The mechanism class "deregulated_nutrient_sensing" is appropriate given the TOR-Pol III connection. The reasoning is well-supported by published literature on Pol III and aging. Confidence of 0.72 is appropriately calibrated.
Raw API responses
solver
{
"reasoning": "let-611 encodes the RPC3 subunit of RNA Polymerase III (Pol III), which is the catalytic core subunit responsible for transcribing small non-coding RNAs including tRNAs, 5S rRNA, and other structural RNAs. Pol III activity is a major anabolic output directly regulated by nutrient-sensing pathways such as TOR (TORC1), and elevated Pol III activity drives ribosome biogenesis and translational capacity. In multiple model organisms including C. elegans, yeast, and Drosophila, reduction of Pol III activity (via subunit knockdown or maf1 overexpression, a Pol III repressor) extends lifespan, while high Pol III activity is associated with shortened lifespan. The normal pro-growth function of RPC3/let-611 thus promotes anabolic signaling that opposes longevity. Its DNA-binding and ssDNA-binding activities are consistent with its role in promoter recognition and transcription initiation at Pol III-dependent genes, reinforcing its role in driving tRNA and ribosomal RNA synthesis downstream of TOR.",
"confidence": 0.72,
"key_pathways": [
"RNA Polymerase III / tRNA transcription",
"TOR (TORC1) nutrient-sensing axis",
"ribosome biogenesis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for let-611 (RNA Pol III subunit RPC3). The mechanistic reasoning is excellent: it correctly identifies that Pol III activity drives tRNA/rRNA synthesis downstream of TOR/TORC1, and that reduction of Pol III activity extends lifespan in multiple organisms including C. elegans. The mechanism class \"deregulated_nutrient_sensing\" is appropriate given the TOR-Pol III connection. The reasoning is well-supported by published literature on Pol III and aging. Confidence of 0.72 is appropriately calibrated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}