TIF1
S. cerevisiae
translation initiation factor eIF4A
What the model saw
Gene: TIF1 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
TIF1 encodes the yeast eIF4A, an ATP-dependent RNA helicase that is an essential component of the eIF4F translation initiation complex. eIF4A unwinds secondary structures in the 5' UTR of mRNAs to facilitate ribosome scanning and translation initiation. Proper eIF4A activity is required for efficient and accurate proteome synthesis; loss of this function impairs global translation and proteostasis, leading to accumulation of misfolded or insufficient proteins. In yeast, robust translation initiation supports stress responses, maintenance of protein quality control networks, and expression of longevity-relevant factors. Furthermore, eIF4A activity is tightly coupled to TOR/nutrient-sensing pathways, where controlled translation is a key downstream effector of pro-longevity signaling. Thus, the normal function of TIF1 supports proteostasis and healthy cellular function, placing it in the pro-longevity category.
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 is based on the general logic that translation initiation factors support proteostasis and healthy cellular function, which would make them pro-longevity. However, TIF1 (eIF4A) is actually anti-longevity in yeast, meaning its deletion or reduction extends lifespan. This is consistent with the well-established finding that reduced translation (including reduced eIF4A activity) extends lifespan in multiple organisms, as it mimics caloric restriction and reduces TOR signaling output. The model actually mentions TOR-regulated translational control but draws the wrong conclusion - reduced translation via TOR inhibition is pro-longevity, meaning the gene itself (which promotes translation) is anti-longevity. The model's reasoning is internally inconsistent and reaches the wrong conclusion with moderate-high confidence (0.72).
Raw API responses
solver
{
"reasoning": "TIF1 encodes the yeast eIF4A, an ATP-dependent RNA helicase that is an essential component of the eIF4F translation initiation complex. eIF4A unwinds secondary structures in the 5' UTR of mRNAs to facilitate ribosome scanning and translation initiation. Proper eIF4A activity is required for efficient and accurate proteome synthesis; loss of this function impairs global translation and proteostasis, leading to accumulation of misfolded or insufficient proteins. In yeast, robust translation initiation supports stress responses, maintenance of protein quality control networks, and expression of longevity-relevant factors. Furthermore, eIF4A activity is tightly coupled to TOR/nutrient-sensing pathways, where controlled translation is a key downstream effector of pro-longevity signaling. Thus, the normal function of TIF1 supports proteostasis and healthy cellular function, placing it in the pro-longevity category.",
"confidence": 0.72,
"key_pathways": [
"eIF4F translation initiation complex",
"mRNA 5' UTR unwinding and ribosome scanning",
"TOR-regulated translational control"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is based on the general logic that translation initiation factors support proteostasis and healthy cellular function, which would make them pro-longevity. However, TIF1 (eIF4A) is actually anti-longevity in yeast, meaning its deletion or reduction extends lifespan. This is consistent with the well-established finding that reduced translation (including reduced eIF4A activity) extends lifespan in multiple organisms, as it mimics caloric restriction and reduces TOR signaling output. The model actually mentions TOR-regulated translational control but draws the wrong conclusion - reduced translation via TOR inhibition is pro-longevity, meaning the gene itself (which promotes translation) is anti-longevity. The model's reasoning is internally inconsistent and reaches the wrong conclusion with moderate-high confidence (0.72).",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}