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ELP4

S. cerevisiae

Elongator subunit ELP4

What the model saw

Gene: ELP4
Organism: Saccharomyces cerevisiae
Known functions: Elongator subunit ELP4. ATP hydrolysis activity. identical protein binding. protein binding. tRNA binding.
View unredacted entry
Elongator subunit ELP4. ATP hydrolysis activity. identical protein binding. protein binding. tRNA binding.

Solver output

Predicted influence
Pro-longevity
Confidence
65%
Mechanism
Epigenetic alterations
Reasoning

ELP4 is a subunit of the Elongator complex, which in yeast is required for wobble uridine (U34) tRNA modification (specifically mcm5s2U34). This tRNA modification is essential for accurate and efficient decoding of AA-ending codons, directly supporting translational fidelity and proteostasis. Loss of Elongator function leads to codon-specific translational errors and proteotoxic stress. Additionally, the Elongator complex has well-established roles in histone H3 acetylation (epigenetic regulation), linking ELP4 to chromatin-level gene expression control. Defects in tRNA modification and translational accuracy are associated with accelerated aging phenotypes in yeast, and proper Elongator function supports stress response pathways. The ATP hydrolysis activity of ELP4 is integral to the ATPase ring subcomplex (ELP4-ELP5-ELP6) that drives tRNA modification catalysis by the ELP1-ELP2-ELP3 subcomplex.

Key pathways
tRNA wobble uridine modification (U34 mcm5s2U)Elongator complex histone H3 acetylationtranslational fidelity and proteostasis
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
Confident wrong
Notes

The model predicted pro_longevity but the ground truth is anti_longevity. ELP4 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model's reasoning about the Elongator complex's role in tRNA modification and histone acetylation is mechanistically sound and detailed, but the model incorrectly concluded that ELP4 supports longevity (pro_longevity) rather than limiting it (anti_longevity). The model assumed that because ELP4 supports important cellular functions (tRNA modification, translational fidelity), its loss would be detrimental to lifespan. However, in yeast, deletion of ELP4 actually extends lifespan, making it anti-longevity. The mechanistic reasoning, while accurate about ELP4's biochemical functions, failed to correctly predict the direction of the longevity effect. The confidence of 0.65 is moderate but still wrong.

Raw API responses

solver

{
  "reasoning": "ELP4 is a subunit of the Elongator complex, which in yeast is required for wobble uridine (U34) tRNA modification (specifically mcm5s2U34). This tRNA modification is essential for accurate and efficient decoding of AA-ending codons, directly supporting translational fidelity and proteostasis. Loss of Elongator function leads to codon-specific translational errors and proteotoxic stress. Additionally, the Elongator complex has well-established roles in histone H3 acetylation (epigenetic regulation), linking ELP4 to chromatin-level gene expression control. Defects in tRNA modification and translational accuracy are associated with accelerated aging phenotypes in yeast, and proper Elongator function supports stress response pathways. The ATP hydrolysis activity of ELP4 is integral to the ATPase ring subcomplex (ELP4-ELP5-ELP6) that drives tRNA modification catalysis by the ELP1-ELP2-ELP3 subcomplex.",
  "confidence": 0.65,
  "key_pathways": [
    "tRNA wobble uridine modification (U34 mcm5s2U)",
    "Elongator complex histone H3 acetylation",
    "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. ELP4 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model's reasoning about the Elongator complex's role in tRNA modification and histone acetylation is mechanistically sound and detailed, but the model incorrectly concluded that ELP4 supports longevity (pro_longevity) rather than limiting it (anti_longevity). The model assumed that because ELP4 supports important cellular functions (tRNA modification, translational fidelity), its loss would be detrimental to lifespan. However, in yeast, deletion of ELP4 actually extends lifespan, making it anti-longevity. The mechanistic reasoning, while accurate about ELP4's biochemical functions, failed to correctly predict the direction of the longevity effect. The confidence of 0.65 is moderate but still wrong.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 3,
  "ground_truth_questionable": false
}