LEU3

S. cerevisiae

leucine-responsive transcriptional regulator LEU3

What the model saw

Gene: LEU3
Organism: Saccharomyces cerevisiae
Known functions: leucine-responsive transcriptional regulator LEU3. DNA-binding transcription activator activity. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity, RNA polymerase II-specific. DNA-binding transcription repressor activity, RNA polymerase II-specific. sequence-specific DNA binding. transcription cis-regulatory region binding. zinc ion binding.

View unredacted entry

leucine-responsive transcriptional regulator LEU3. DNA-binding transcription activator activity. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity, RNA polymerase II-specific. DNA-binding transcription repressor activity, RNA polymerase II-specific. sequence-specific DNA binding. transcription cis-regulatory region binding. zinc ion binding.

Solver output

Predicted influence

Unclear

Confidence

42%

Mechanism

Deregulated nutrient sensing

Reasoning

LEU3 is a zinc finger transcription factor that acts as both an activator and repressor of RNA Pol II-dependent genes, switching roles depending on the availability of α-isopropylmalate (α-IPM), an intermediate in leucine biosynthesis. When leucine is abundant, α-IPM levels drop and LEU3 acts as a repressor; when leucine is limiting, α-IPM accumulates and converts LEU3 into a transcriptional activator of branched-chain amino acid biosynthesis genes (LEU1, LEU2, LEU4, ILV2, ILV3, ILV5). This dual activator/repressor role couples amino acid availability to transcriptional output, placing LEU3 within nutrient-sensing circuitry. However, its net effect on longevity is ambiguous: promoting leucine biosynthesis could activate TORC1 signaling (anti-longevity), but LEU3 also regulates genes involved in mitochondrial function and other metabolic processes. The context-dependent switch between activation and repression, and the breadth of its transcriptional targets, makes a definitive pro- or anti-longevity assignment difficult without direct lifespan data.

Key pathways

branched-chain amino acid biosynthesis (LEU/ILV genes)TORC1 nutrient sensing via leucine availabilityα-isopropylmalate-dependent transcriptional switching

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

3/5

Failure mode

Appropriately uncertain

Notes

The model predicted "unclear" while the ground truth is "anti_longevity." The model's reasoning about LEU3's biochemical function (α-IPM-dependent transcriptional switching, dual activator/repressor role, connection to leucine biosynthesis and TORC1) is mechanistically sound and shows good domain knowledge. The model even correctly identified the TORC1/anti-longevity pathway as a possibility but hedged too much and ultimately declined to commit to a prediction. The model's confidence was appropriately low (0.42), but it still failed to arrive at the correct answer. The mechanism reasoning was partially correct in identifying the anti-longevity pathway (TORC1 activation via leucine) but didn't commit to it. This is a case of appropriate uncertainty that nonetheless resulted in a wrong answer.

Raw API responses

solver

{
  "reasoning": "LEU3 is a zinc finger transcription factor that acts as both an activator and repressor of RNA Pol II-dependent genes, switching roles depending on the availability of α-isopropylmalate (α-IPM), an intermediate in leucine biosynthesis. When leucine is abundant, α-IPM levels drop and LEU3 acts as a repressor; when leucine is limiting, α-IPM accumulates and converts LEU3 into a transcriptional activator of branched-chain amino acid biosynthesis genes (LEU1, LEU2, LEU4, ILV2, ILV3, ILV5). This dual activator/repressor role couples amino acid availability to transcriptional output, placing LEU3 within nutrient-sensing circuitry. However, its net effect on longevity is ambiguous: promoting leucine biosynthesis could activate TORC1 signaling (anti-longevity), but LEU3 also regulates genes involved in mitochondrial function and other metabolic processes. The context-dependent switch between activation and repression, and the breadth of its transcriptional targets, makes a definitive pro- or anti-longevity assignment difficult without direct lifespan data.",
  "confidence": 0.42,
  "key_pathways": [
    "branched-chain amino acid biosynthesis (LEU/ILV genes)",
    "TORC1 nutrient sensing via leucine availability",
    "α-isopropylmalate-dependent transcriptional switching"
  ],
  "mechanism_class": "deregulated_nutrient_sensing",
  "longevity_influence": "unclear"
}

advisor

{
  "notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about LEU3's biochemical function (α-IPM-dependent transcriptional switching, dual activator/repressor role, connection to leucine biosynthesis and TORC1) is mechanistically sound and shows good domain knowledge. The model even correctly identified the TORC1/anti-longevity pathway as a possibility but hedged too much and ultimately declined to commit to a prediction. The model's confidence was appropriately low (0.42), but it still failed to arrive at the correct answer. The mechanism reasoning was partially correct in identifying the anti-longevity pathway (TORC1 activation via leucine) but didn't commit to it. This is a case of appropriate uncertainty that nonetheless resulted in a wrong answer.",
  "failure_mode": "appropriately_uncertain",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}