IKI3
S. cerevisiae
Elongator subunit IKI3
What the model saw
Gene: IKI3 Organism: Saccharomyces cerevisiae Known functions: Elongator subunit IKI3. identical protein binding. protein binding. tRNA binding.
View unredacted entry
Elongator subunit IKI3. identical protein binding. protein binding. tRNA binding.
Solver output
IKI3 encodes the largest subunit (Elp1/IKI3) of the Elongator complex in S. cerevisiae, which functions as a histone acetyltransferase complex and is critical for tRNA wobble uridine modification (mcm5s2U34). The tRNA modification role is particularly relevant: proper tRNA modification by Elongator ensures accurate and efficient translation of codon-biased mRNAs, including those encoding stress-response and proteostasis factors. Loss of Elongator-dependent tRNA modifications leads to translational errors and proteotoxic stress, implicating IKI3 in maintaining proteostasis. Additionally, Elongator's histone H3 acetylation activity at gene bodies supports proper transcriptional elongation, contributing to epigenetic regulation. Defects in Elongator function are associated with reduced fitness and stress sensitivity in yeast, suggesting the normal function of IKI3 supports longevity through both epigenetic and translational fidelity mechanisms.
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 about IKI3/Elp1 being part of the Elongator complex and its roles in tRNA modification and histone acetyltransferase activity is mechanistically accurate, but the model drew the wrong conclusion about the longevity influence. In yeast, IKI3 (Elp1) is anti-longevity, meaning its deletion or loss extends lifespan rather than shortening it. The model assumed that because Elongator supports proteostasis and stress response, it must be pro-longevity, but this is incorrect - IKI3 appears to limit lifespan. The model had moderate confidence (0.62) but still got the direction wrong. The mechanistic reasoning about Elongator's functions is largely correct, but the interpretation of how those functions relate to longevity is wrong.
Raw API responses
solver
{
"reasoning": "IKI3 encodes the largest subunit (Elp1/IKI3) of the Elongator complex in S. cerevisiae, which functions as a histone acetyltransferase complex and is critical for tRNA wobble uridine modification (mcm5s2U34). The tRNA modification role is particularly relevant: proper tRNA modification by Elongator ensures accurate and efficient translation of codon-biased mRNAs, including those encoding stress-response and proteostasis factors. Loss of Elongator-dependent tRNA modifications leads to translational errors and proteotoxic stress, implicating IKI3 in maintaining proteostasis. Additionally, Elongator's histone H3 acetylation activity at gene bodies supports proper transcriptional elongation, contributing to epigenetic regulation. Defects in Elongator function are associated with reduced fitness and stress sensitivity in yeast, suggesting the normal function of IKI3 supports longevity through both epigenetic and translational fidelity mechanisms.",
"confidence": 0.62,
"key_pathways": [
"Elongator complex tRNA wobble uridine modification (mcm5s2U34)",
"Histone H3 acetyltransferase / transcriptional elongation",
"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. The model's reasoning about IKI3/Elp1 being part of the Elongator complex and its roles in tRNA modification and histone acetyltransferase activity is mechanistically accurate, but the model drew the wrong conclusion about the longevity influence. In yeast, IKI3 (Elp1) is anti-longevity, meaning its deletion or loss extends lifespan rather than shortening it. The model assumed that because Elongator supports proteostasis and stress response, it must be pro-longevity, but this is incorrect - IKI3 appears to limit lifespan. The model had moderate confidence (0.62) but still got the direction wrong. The mechanistic reasoning about Elongator's functions is largely correct, but the interpretation of how those functions relate to longevity is wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}