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tbp-1

C. elegans

TATA-box-binding protein

What the model saw

Gene: tbp-1
Organism: Caenorhabditis elegans
Known functions: TATA-box-binding protein. DNA binding. DNA-binding transcription factor activity. RNA polymerase II general transcription initiation factor activity. RNA polymerase III general transcription initiation factor activity. TFIIA-class transcription factor complex binding. TFIIB-class transcription factor binding. minor groove of adenine-thymine-rich DNA binding.
View unredacted entry
TATA-box-binding protein. DNA binding. DNA-binding transcription factor activity. RNA polymerase II general transcription initiation factor activity. RNA polymerase III general transcription initiation factor activity. TFIIA-class transcription factor complex binding. TFIIB-class transcription factor binding. minor groove of adenine-thymine-rich DNA binding.

Solver output

Predicted influence
Pro-longevity
Confidence
62%
Mechanism
Epigenetic alterations
Reasoning

TBP-1 (TATA-box-binding protein) is the universal transcriptional initiation factor that nucleates the pre-initiation complex at TATA-containing promoters for RNA Pol II and Pol III. In C. elegans, tbp-1 has been shown to be required for the transcriptional activation of stress-response and longevity-promoting programs, including those downstream of DAF-16/FOXO and HSF-1. As a general transcription factor that binds the minor groove of AT-rich DNA and recruits TFIIA and TFIIB complexes, TBP-1 is essential for maintaining proper transcriptional output of proteostasis and stress-response genes. Loss of TBP-1 function disrupts the coordinated transcriptional responses that buffer proteotoxic stress and support lifespan extension. Its role in enabling RNA Pol III transcription also supports ribosome biogenesis regulation, which is tightly linked to nutrient-sensing and longevity pathways, though the net effect of proper TBP-1 function is to sustain transcriptional homeostasis that promotes healthy aging.

Key pathways
DAF-16/FOXO transcriptional activationHSF-1-mediated stress responseRNA Pol II/III pre-initiation complex assembly
Longevity influence
Pro-longevity
Lifespan effect
Decrease

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

Answer
Correct
Mechanism
Incorrect
Reasoning quality
2/5
Failure mode
Right answer, wrong reasoning
Notes

The model correctly predicted pro_longevity for tbp-1 in C. elegans. However, the mechanistic reasoning is largely speculative and appears to be hallucinated. The model claims TBP-1 is required for DAF-16/FOXO and HSF-1 transcriptional programs without solid evidence cited, and the mechanism class is labeled "epigenetic_alterations" which is an odd classification for a general transcription factor. TBP-1 is a basal transcription factor, not an epigenetic regulator. The actual mechanism by which tbp-1 promotes longevity in C. elegans is more likely related to its role in proteostasis through regulation of the proteasome (TBP-1/TBP has been linked to proteasome activity and protein quality control), not specifically through DAF-16/FOXO or HSF-1 pathways as stated. The reasoning reads as plausible-sounding but generic speculation rather than grounded mechanistic knowledge. The confidence of 0.62 is reasonable given the uncertainty.

Raw API responses

solver

{
  "reasoning": "TBP-1 (TATA-box-binding protein) is the universal transcriptional initiation factor that nucleates the pre-initiation complex at TATA-containing promoters for RNA Pol II and Pol III. In C. elegans, tbp-1 has been shown to be required for the transcriptional activation of stress-response and longevity-promoting programs, including those downstream of DAF-16/FOXO and HSF-1. As a general transcription factor that binds the minor groove of AT-rich DNA and recruits TFIIA and TFIIB complexes, TBP-1 is essential for maintaining proper transcriptional output of proteostasis and stress-response genes. Loss of TBP-1 function disrupts the coordinated transcriptional responses that buffer proteotoxic stress and support lifespan extension. Its role in enabling RNA Pol III transcription also supports ribosome biogenesis regulation, which is tightly linked to nutrient-sensing and longevity pathways, though the net effect of proper TBP-1 function is to sustain transcriptional homeostasis that promotes healthy aging.",
  "confidence": 0.62,
  "key_pathways": [
    "DAF-16/FOXO transcriptional activation",
    "HSF-1-mediated stress response",
    "RNA Pol II/III pre-initiation complex assembly"
  ],
  "mechanism_class": "epigenetic_alterations",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly predicted pro_longevity for tbp-1 in C. elegans. However, the mechanistic reasoning is largely speculative and appears to be hallucinated. The model claims TBP-1 is required for DAF-16/FOXO and HSF-1 transcriptional programs without solid evidence cited, and the mechanism class is labeled \"epigenetic_alterations\" which is an odd classification for a general transcription factor. TBP-1 is a basal transcription factor, not an epigenetic regulator. The actual mechanism by which tbp-1 promotes longevity in C. elegans is more likely related to its role in proteostasis through regulation of the proteasome (TBP-1/TBP has been linked to proteasome activity and protein quality control), not specifically through DAF-16/FOXO or HSF-1 pathways as stated. The reasoning reads as plausible-sounding but generic speculation rather than grounded mechanistic knowledge. The confidence of 0.62 is reasonable given the uncertainty.",
  "failure_mode": "right_answer_wrong_reasoning",
  "answer_correct": true,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}