rpb-8
C. elegans
putative DNA-directed RNA polymerases I, II, and III subunit RPABC3
What the model saw
Gene: rpb-8 Organism: Caenorhabditis elegans Known functions: putative DNA-directed RNA polymerases I, II, and III subunit RPABC3. DNA-directed RNA polymerase activity. protein binding.
View unredacted entry
putative DNA-directed RNA polymerases I, II, and III subunit RPABC3. DNA-directed RNA polymerase activity. protein binding.
Solver output
rpb-8 encodes a shared subunit (RPABC3/RPB8) of RNA polymerases I, II, and III, which are essential for transcription of rRNA, mRNA, and small structural RNAs respectively. Proper transcriptional output is required to maintain gene expression homeostasis, including expression of stress-response, proteostasis, and longevity-associated genes. In C. elegans, global transcriptional fidelity and the ability to mount transcriptional responses to stress are tightly linked to lifespan; loss of core transcriptional machinery components typically shortens lifespan by impairing these responses. As a shared polymerase subunit, rpb-8 supports the epigenetic/transcriptional regulatory layer that governs aging-related gene programs, most closely mapping to epigenetic alterations (transcriptional dysregulation) among the hallmarks of aging. Its normal function therefore supports, rather than 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that because rpb-8 is a core transcriptional subunit, its normal function must support longevity. However, the ground truth indicates rpb-8 is anti_longevity, meaning its activity actually opposes longevity (i.e., knockdown/loss of rpb-8 extends lifespan). This is consistent with findings in C. elegans where reducing global transcription/translation rates (e.g., via RNA Pol II subunit knockdown) can extend lifespan by reducing biosynthetic load and activating stress responses. The model's mechanistic reasoning was backwards - it assumed essential genes must be pro-longevity, but in C. elegans, reducing activity of core transcriptional machinery can be beneficial for lifespan. The confidence of 0.55 was relatively low, but the prediction was still wrong in direction.
Raw API responses
solver
{
"reasoning": "rpb-8 encodes a shared subunit (RPABC3/RPB8) of RNA polymerases I, II, and III, which are essential for transcription of rRNA, mRNA, and small structural RNAs respectively. Proper transcriptional output is required to maintain gene expression homeostasis, including expression of stress-response, proteostasis, and longevity-associated genes. In C. elegans, global transcriptional fidelity and the ability to mount transcriptional responses to stress are tightly linked to lifespan; loss of core transcriptional machinery components typically shortens lifespan by impairing these responses. As a shared polymerase subunit, rpb-8 supports the epigenetic/transcriptional regulatory layer that governs aging-related gene programs, most closely mapping to epigenetic alterations (transcriptional dysregulation) among the hallmarks of aging. Its normal function therefore supports, rather than opposes, longevity.",
"confidence": 0.55,
"key_pathways": [
"RNA Pol I/II/III transcription",
"transcriptional stress response",
"gene expression homeostasis"
],
"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 assumed that because rpb-8 is a core transcriptional subunit, its normal function must support longevity. However, the ground truth indicates rpb-8 is anti_longevity, meaning its activity actually opposes longevity (i.e., knockdown/loss of rpb-8 extends lifespan). This is consistent with findings in C. elegans where reducing global transcription/translation rates (e.g., via RNA Pol II subunit knockdown) can extend lifespan by reducing biosynthetic load and activating stress responses. The model's mechanistic reasoning was backwards - it assumed essential genes must be pro-longevity, but in C. elegans, reducing activity of core transcriptional machinery can be beneficial for lifespan. The confidence of 0.55 was relatively low, but the prediction was still wrong in direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}