TIF4632
S. cerevisiae
translation initiation factor eIF4G
What the model saw
Gene: TIF4632 Organism: Saccharomyces cerevisiae Known functions: translation initiation factor eIF4G. ATPase activator activity. RNA binding. mRNA binding. protein binding. translation initiation factor activity. translation initiation factor binding.
View unredacted entry
translation initiation factor eIF4G. ATPase activator activity. RNA binding. mRNA binding. protein binding. translation initiation factor activity. translation initiation factor binding.
Solver output
TIF4632 encodes eIF4G, a central scaffold of the eIF4F translation initiation complex in yeast. eIF4G coordinates cap-dependent mRNA translation by bridging eIF4E (cap-binding), eIF4A (RNA helicase/ATPase, which TIF4632 activates), and the 43S pre-initiation complex. Elevated global translation driven by eIF4G activity is downstream of TORC1 signaling, a key nutrient-sensing axis where hyperactivation shortens lifespan. Reducing eIF4G function (or globally dampening cap-dependent translation) is well-established to extend replicative and chronological lifespan in yeast, paralleling the pro-longevity effects of TOR inhibition. Thus, the normal pro-translational function of TIF4632 opposes longevity by sustaining high anabolic flux that accelerates aging.
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 correctly predicted anti_longevity for TIF4632. The mechanistic reasoning is sound and well-articulated: TIF4632 encodes eIF4G, a scaffold of the eIF4F translation initiation complex, and its pro-translational activity is downstream of TORC1 nutrient sensing. The model correctly identifies that reducing eIF4G function extends lifespan in yeast, making TIF4632 anti-longevity. The connection to TORC1/TOR signaling and cap-dependent translation is accurate and well-supported by the literature. Confidence of 0.75 is appropriate given the indirect nature of the evidence.
Raw API responses
solver
{
"reasoning": "TIF4632 encodes eIF4G, a central scaffold of the eIF4F translation initiation complex in yeast. eIF4G coordinates cap-dependent mRNA translation by bridging eIF4E (cap-binding), eIF4A (RNA helicase/ATPase, which TIF4632 activates), and the 43S pre-initiation complex. Elevated global translation driven by eIF4G activity is downstream of TORC1 signaling, a key nutrient-sensing axis where hyperactivation shortens lifespan. Reducing eIF4G function (or globally dampening cap-dependent translation) is well-established to extend replicative and chronological lifespan in yeast, paralleling the pro-longevity effects of TOR inhibition. Thus, the normal pro-translational function of TIF4632 opposes longevity by sustaining high anabolic flux that accelerates aging.",
"confidence": 0.75,
"key_pathways": [
"TORC1-eIF4F cap-dependent translation",
"eIF4G scaffold assembly (eIF4E-eIF4G-eIF4A)",
"nutrient sensing / TOR signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for TIF4632. The mechanistic reasoning is sound and well-articulated: TIF4632 encodes eIF4G, a scaffold of the eIF4F translation initiation complex, and its pro-translational activity is downstream of TORC1 nutrient sensing. The model correctly identifies that reducing eIF4G function extends lifespan in yeast, making TIF4632 anti-longevity. The connection to TORC1/TOR signaling and cap-dependent translation is accurate and well-supported by the literature. Confidence of 0.75 is appropriate given the indirect nature of the evidence.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}