f26e4.4
C. elegans
DNA-directed RNA polymerase III subunit RPC4
What the model saw
Gene: F26E4.4 Organism: Caenorhabditis elegans Known functions: DNA-directed RNA polymerase III subunit RPC4. DNA binding.
View unredacted entry
DNA-directed RNA polymerase III subunit RPC4. DNA binding.
Solver output
F26E4.4 encodes RPC4, a subunit of RNA Polymerase III (Pol III), which is responsible for transcribing small non-coding RNAs including tRNAs and 5S rRNA. Pol III activity is a major downstream effector of TORC1 (TOR complex 1) signaling — a central nutrient-sensing pathway — and elevated Pol III activity promotes anabolic growth and protein synthesis capacity. In C. elegans and other model organisms, reduced Pol III activity (e.g., via RPC1/rpc-1 or associated subunit knockdown) extends lifespan, phenocopying reduced TOR signaling. Conversely, normal/high Pol III activity sustains elevated translational capacity, which is associated with shortened lifespan. Thus, the normal pro-growth function of RPC4/Pol III opposes longevity by maintaining high tRNA output and ribosome biogenesis 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 F26E4.4 (RPC4, RNA Pol III subunit). The mechanistic reasoning is sound and well-articulated: Pol III activity is downstream of TORC1 nutrient sensing, promotes tRNA synthesis and translational capacity, and its reduction extends lifespan in C. elegans. The model correctly identifies that normal/high Pol III activity opposes longevity, making it anti-longevity. The confidence of 0.72 is appropriate given the indirect nature of the evidence. Overall, this is an excellent prediction with correct answer and correct mechanism.
Raw API responses
solver
{
"reasoning": "F26E4.4 encodes RPC4, a subunit of RNA Polymerase III (Pol III), which is responsible for transcribing small non-coding RNAs including tRNAs and 5S rRNA. Pol III activity is a major downstream effector of TORC1 (TOR complex 1) signaling — a central nutrient-sensing pathway — and elevated Pol III activity promotes anabolic growth and protein synthesis capacity. In C. elegans and other model organisms, reduced Pol III activity (e.g., via RPC1/rpc-1 or associated subunit knockdown) extends lifespan, phenocopying reduced TOR signaling. Conversely, normal/high Pol III activity sustains elevated translational capacity, which is associated with shortened lifespan. Thus, the normal pro-growth function of RPC4/Pol III opposes longevity by maintaining high tRNA output and ribosome biogenesis downstream of nutrient-sensing pathways.",
"confidence": 0.72,
"key_pathways": [
"RNA Polymerase III / tRNA transcription",
"TOR (TORC1) nutrient-sensing signaling",
"ribosome biogenesis and translational capacity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for F26E4.4 (RPC4, RNA Pol III subunit). The mechanistic reasoning is sound and well-articulated: Pol III activity is downstream of TORC1 nutrient sensing, promotes tRNA synthesis and translational capacity, and its reduction extends lifespan in C. elegans. The model correctly identifies that normal/high Pol III activity opposes longevity, making it anti-longevity. The confidence of 0.72 is appropriate given the indirect nature of the evidence. Overall, this is an excellent prediction with correct answer and correct mechanism.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}