RPO31
S. cerevisiae
DNA-directed RNA polymerase III core subunit RPO31
What the model saw
Gene: RPO31 Organism: Saccharomyces cerevisiae Known functions: DNA-directed RNA polymerase III core subunit RPO31. 5'-3' RNA polymerase activity. DNA binding. DNA-directed RNA polymerase activity. protein binding. zinc ion binding.
View unredacted entry
DNA-directed RNA polymerase III core subunit RPO31. 5'-3' RNA polymerase activity. DNA binding. DNA-directed RNA polymerase activity. protein binding. zinc ion binding.
Solver output
RPO31 encodes the largest (catalytic) subunit of RNA Polymerase III in S. cerevisiae, responsible for transcribing small non-coding RNAs including tRNAs, 5S rRNA, and other short structural RNAs. Proper tRNA synthesis is essential for translational fidelity and proteostasis; loss of Pol III activity impairs ribosome biogenesis and global translation capacity. However, in the context of aging, Pol III activity is tightly regulated by TORC1 signaling — hyperactivation of Pol III (e.g., via excess tRNA production) promotes anabolic growth and accelerates aging, while its repression extends lifespan. The normal, basal function of RPO31 is required for cellular viability and maintenance of the non-coding RNA landscape, which supports proteostasis and cellular homeostasis. Because the gene's normal function is necessary for cell survival and balanced gene expression rather than being a driver of aging per se, and because Pol III is a downstream effector of nutrient-sensing pathways (TOR), its regulated activity is net pro-longevity at physiological levels, though overactivation would be anti-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 predicted "pro_longevity" but the ground truth is "anti_longevity." The model's reasoning actually acknowledges that Pol III hyperactivation promotes aging and that its repression extends lifespan — which is consistent with RPO31 being anti-longevity (i.e., its normal activity drives aging). However, the model then contradicts itself by concluding that RPO31 is pro-longevity because "basal function is required for cellular viability." This conflates essentiality with pro-longevity classification. The GenAge classification of anti_longevity aligns with the well-established finding that reducing Pol III activity (e.g., partial loss-of-function of RPO31) extends lifespan in yeast, consistent with the TOR/Pol III aging axis. The model's mechanistic understanding was partially correct (it correctly identified the TOR-Pol III connection and that Pol III repression extends lifespan), but it drew the wrong conclusion from its own reasoning. The confidence of 0.55 reflects some uncertainty, but the final answer is still wrong.
Raw API responses
solver
{
"reasoning": "RPO31 encodes the largest (catalytic) subunit of RNA Polymerase III in S. cerevisiae, responsible for transcribing small non-coding RNAs including tRNAs, 5S rRNA, and other short structural RNAs. Proper tRNA synthesis is essential for translational fidelity and proteostasis; loss of Pol III activity impairs ribosome biogenesis and global translation capacity. However, in the context of aging, Pol III activity is tightly regulated by TORC1 signaling — hyperactivation of Pol III (e.g., via excess tRNA production) promotes anabolic growth and accelerates aging, while its repression extends lifespan. The normal, basal function of RPO31 is required for cellular viability and maintenance of the non-coding RNA landscape, which supports proteostasis and cellular homeostasis. Because the gene's normal function is necessary for cell survival and balanced gene expression rather than being a driver of aging per se, and because Pol III is a downstream effector of nutrient-sensing pathways (TOR), its regulated activity is net pro-longevity at physiological levels, though overactivation would be anti-longevity.",
"confidence": 0.55,
"key_pathways": [
"RNA Polymerase III transcription (tRNA/5S rRNA synthesis)",
"TORC1-regulated nutrient sensing",
"translational fidelity and proteostasis"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning actually acknowledges that Pol III hyperactivation promotes aging and that its repression extends lifespan — which is consistent with RPO31 being anti-longevity (i.e., its normal activity drives aging). However, the model then contradicts itself by concluding that RPO31 is pro-longevity because \"basal function is required for cellular viability.\" This conflates essentiality with pro-longevity classification. The GenAge classification of anti_longevity aligns with the well-established finding that reducing Pol III activity (e.g., partial loss-of-function of RPO31) extends lifespan in yeast, consistent with the TOR/Pol III aging axis. The model's mechanistic understanding was partially correct (it correctly identified the TOR-Pol III connection and that Pol III repression extends lifespan), but it drew the wrong conclusion from its own reasoning. The confidence of 0.55 reflects some uncertainty, but the final answer is still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}