TIF2
S. cerevisiae
translation initiation factor eIF4A
What the model saw
Gene: TIF2 Organism: Saccharomyces cerevisiae Known functions: translation initiation factor eIF4A. ATP binding. ATP hydrolysis activity. ATP-dependent activity, acting on RNA. RNA helicase activity. nucleic acid binding. protein binding. translation initiation factor activity.
View unredacted entry
translation initiation factor eIF4A. ATP binding. ATP hydrolysis activity. ATP-dependent activity, acting on RNA. RNA helicase activity. nucleic acid binding. protein binding. translation initiation factor activity.
Solver output
TIF2 encodes the yeast translation initiation factor eIF4A, an ATP-dependent RNA helicase that unwinds secondary structures in the 5' UTR of mRNAs to facilitate ribosome scanning and translation initiation. Efficient and accurate translation initiation is a central pillar of proteostasis; eIF4A activity ensures that the proteome is synthesized correctly and that stress-response and housekeeping proteins are produced at appropriate levels. Loss of eIF4A function impairs global protein synthesis and proteostasis maintenance, which is a hallmark of aging. In yeast, robust translation initiation supports the production of chaperones and other quality-control factors that counteract protein aggregation and cellular damage accumulating with age. Additionally, eIF4A-mediated translation is required for proper expression of nutrient-sensing pathway components (e.g., TOR pathway effectors), linking it indirectly to lifespan regulation through deregulated nutrient sensing as well.
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 TIF2 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. TIF2 encodes eIF4A, a translation initiation factor. The model reasoned that efficient translation initiation supports proteostasis and longevity, but in reality TIF2 is anti-longevity in yeast — meaning its activity works against longevity (i.e., deletion or reduction of TIF2 extends lifespan). This is consistent with the broader finding that reduced translation/protein synthesis (e.g., via reduced TOR signaling or reduced eIF4A activity) extends lifespan in yeast and other organisms. The model's reasoning was plausible on the surface but missed the key insight that reduced translation initiation is actually beneficial for longevity, not detrimental. The model conflated "important for cellular function" with "pro-longevity," which is a common error. The confidence of 0.72 makes this a notably wrong prediction.
Raw API responses
solver
{
"reasoning": "TIF2 encodes the yeast translation initiation factor eIF4A, an ATP-dependent RNA helicase that unwinds secondary structures in the 5' UTR of mRNAs to facilitate ribosome scanning and translation initiation. Efficient and accurate translation initiation is a central pillar of proteostasis; eIF4A activity ensures that the proteome is synthesized correctly and that stress-response and housekeeping proteins are produced at appropriate levels. Loss of eIF4A function impairs global protein synthesis and proteostasis maintenance, which is a hallmark of aging. In yeast, robust translation initiation supports the production of chaperones and other quality-control factors that counteract protein aggregation and cellular damage accumulating with age. Additionally, eIF4A-mediated translation is required for proper expression of nutrient-sensing pathway components (e.g., TOR pathway effectors), linking it indirectly to lifespan regulation through deregulated nutrient sensing as well.",
"confidence": 0.72,
"key_pathways": [
"eIF4F translation initiation complex",
"mRNA 5' UTR unwinding and ribosome scanning",
"proteostasis and protein quality control"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted TIF2 as pro_longevity with 0.72 confidence, but the ground truth is anti_longevity. TIF2 encodes eIF4A, a translation initiation factor. The model reasoned that efficient translation initiation supports proteostasis and longevity, but in reality TIF2 is anti-longevity in yeast — meaning its activity works against longevity (i.e., deletion or reduction of TIF2 extends lifespan). This is consistent with the broader finding that reduced translation/protein synthesis (e.g., via reduced TOR signaling or reduced eIF4A activity) extends lifespan in yeast and other organisms. The model's reasoning was plausible on the surface but missed the key insight that reduced translation initiation is actually beneficial for longevity, not detrimental. The model conflated \"important for cellular function\" with \"pro-longevity,\" which is a common error. The confidence of 0.72 makes this a notably wrong prediction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}