Polr3D
D. melanogaster
RNA polymerase III subunit D
What the model saw
Gene: Polr3D Organism: Drosophila melanogaster Known functions: RNA polymerase III subunit D. DNA binding.
View unredacted entry
RNA polymerase III subunit D. DNA binding.
Solver output
Polr3D encodes a subunit of RNA Polymerase III (Pol III), the enzyme 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, particularly TOR (Target of Rapamycin) signaling — elevated TOR activity upregulates Pol III to boost translational capacity. Increased Pol III activity promotes cellular growth and protein synthesis but is associated with accelerated aging; conversely, reduced Pol III activity extends lifespan in multiple model organisms including yeast, worms, and flies, likely by mimicking caloric restriction and dampening TOR-driven anabolism. As a core structural/catalytic subunit of Pol III, Polr3D is required for full Pol III transcriptional output, meaning its normal function sustains the pro-aging, TOR-coupled anabolic program. The DNA-binding activity of this subunit contributes to promoter recognition and transcription initiation at Pol III target genes, further linking it to the nutrient-sensing/growth axis that opposes longevity.
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 Polr3D. The mechanistic reasoning is well-grounded: Pol III activity is indeed regulated by TOR signaling, and reduced Pol III activity has been shown to extend lifespan in multiple model organisms including Drosophila. The model correctly identifies the connection between Pol III transcription (tRNA/5S rRNA synthesis), nutrient sensing via TOR, and the pro-aging anabolic program. The reasoning is coherent, specific, and well-supported by the literature on Pol III and aging. Confidence of 0.72 is appropriate given the limited information provided in the entry.
Raw API responses
solver
{
"reasoning": "Polr3D encodes a subunit of RNA Polymerase III (Pol III), the enzyme 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, particularly TOR (Target of Rapamycin) signaling — elevated TOR activity upregulates Pol III to boost translational capacity. Increased Pol III activity promotes cellular growth and protein synthesis but is associated with accelerated aging; conversely, reduced Pol III activity extends lifespan in multiple model organisms including yeast, worms, and flies, likely by mimicking caloric restriction and dampening TOR-driven anabolism. As a core structural/catalytic subunit of Pol III, Polr3D is required for full Pol III transcriptional output, meaning its normal function sustains the pro-aging, TOR-coupled anabolic program. The DNA-binding activity of this subunit contributes to promoter recognition and transcription initiation at Pol III target genes, further linking it to the nutrient-sensing/growth axis that opposes longevity.",
"confidence": 0.72,
"key_pathways": [
"RNA Polymerase III transcription (tRNA/5S rRNA synthesis)",
"TOR signaling / nutrient sensing",
"translational capacity regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Polr3D. The mechanistic reasoning is well-grounded: Pol III activity is indeed regulated by TOR signaling, and reduced Pol III activity has been shown to extend lifespan in multiple model organisms including Drosophila. The model correctly identifies the connection between Pol III transcription (tRNA/5S rRNA synthesis), nutrient sensing via TOR, and the pro-aging anabolic program. The reasoning is coherent, specific, and well-supported by the literature on Pol III and aging. Confidence of 0.72 is appropriate given the limited information provided in the entry.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}