ELP3
S. cerevisiae
Elongator subunit ELP3
What the model saw
Gene: ELP3 Organism: Saccharomyces cerevisiae Known functions: Elongator subunit ELP3. acyltransferase activity, transferring groups other than amino-acyl groups. catalytic activity. histone acetyltransferase activity. iron-sulfur cluster binding. protein binding. tRNA uridine(34) acetyltransferase activity.
View unredacted entry
Elongator subunit ELP3. acyltransferase activity, transferring groups other than amino-acyl groups. catalytic activity. histone acetyltransferase activity. iron-sulfur cluster binding. protein binding. tRNA uridine(34) acetyltransferase activity.
Solver output
ELP3 is the catalytic subunit of the Elongator complex, harboring histone acetyltransferase (HAT) activity that targets histones H3 and H4, contributing to transcriptional elongation and chromatin remodeling. Proper histone acetylation patterns are essential for maintaining epigenetic homeostasis, and loss of Elongator function leads to dysregulated gene expression associated with aging phenotypes. Additionally, ELP3's tRNA uridine(34) acetyltransferase activity modifies wobble-position uridines (mcm5U34), which is critical for translational fidelity and proteostasis — loss of this modification causes ribosomal frameshifting and protein aggregation, a hallmark of cellular aging. The iron-sulfur cluster binding is required for the tRNA modification activity, linking redox chemistry to translational accuracy. Together, both the epigenetic (HAT) and translational fidelity (tRNA modification) roles of ELP3 support cellular health and oppose aging-associated deterioration, making its normal function pro-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 ELP3 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is plausible in general terms — ELP3 does have histone acetyltransferase and tRNA modification activities — but the model incorrectly inferred that these functions would make ELP3 pro-longevity. In yeast, ELP3 (as part of the Elongator complex) is anti-longevity, meaning its deletion or loss of function extends lifespan rather than shortening it. The model's mechanistic reasoning, while technically accurate about ELP3's molecular functions, incorrectly extrapolated that these functions oppose aging. The model was fairly confident (0.72) in the wrong direction. The reasoning quality is moderate — it demonstrates good knowledge of ELP3's molecular biology but fails to correctly predict the direction of longevity influence in yeast.
Raw API responses
solver
{
"reasoning": "ELP3 is the catalytic subunit of the Elongator complex, harboring histone acetyltransferase (HAT) activity that targets histones H3 and H4, contributing to transcriptional elongation and chromatin remodeling. Proper histone acetylation patterns are essential for maintaining epigenetic homeostasis, and loss of Elongator function leads to dysregulated gene expression associated with aging phenotypes. Additionally, ELP3's tRNA uridine(34) acetyltransferase activity modifies wobble-position uridines (mcm5U34), which is critical for translational fidelity and proteostasis — loss of this modification causes ribosomal frameshifting and protein aggregation, a hallmark of cellular aging. The iron-sulfur cluster binding is required for the tRNA modification activity, linking redox chemistry to translational accuracy. Together, both the epigenetic (HAT) and translational fidelity (tRNA modification) roles of ELP3 support cellular health and oppose aging-associated deterioration, making its normal function pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"Elongator complex histone acetyltransferase / chromatin remodeling",
"tRNA wobble uridine modification (mcm5U34) and translational fidelity",
"Proteostasis maintenance via accurate mRNA decoding"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted ELP3 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is plausible in general terms — ELP3 does have histone acetyltransferase and tRNA modification activities — but the model incorrectly inferred that these functions would make ELP3 pro-longevity. In yeast, ELP3 (as part of the Elongator complex) is anti-longevity, meaning its deletion or loss of function extends lifespan rather than shortening it. The model's mechanistic reasoning, while technically accurate about ELP3's molecular functions, incorrectly extrapolated that these functions oppose aging. The model was fairly confident (0.72) in the wrong direction. The reasoning quality is moderate — it demonstrates good knowledge of ELP3's molecular biology but fails to correctly predict the direction of longevity influence in yeast.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}