TIF4631
S. cerevisiae
translation initiation factor eIF4G
What the model saw
Gene: TIF4631 Organism: Saccharomyces cerevisiae Known functions: translation initiation factor eIF4G. ATPase activator activity. RNA binding. mRNA binding. molecular condensate scaffold activity. protein binding. translation initiation factor activity.
View unredacted entry
translation initiation factor eIF4G. ATPase activator activity. RNA binding. mRNA binding. molecular condensate scaffold activity. protein binding. translation initiation factor activity.
Solver output
TIF4631 encodes the yeast eIF4G homolog, a central scaffold of the eIF4F translation initiation complex that recruits the 43S pre-initiation complex to the 5' cap of mRNAs. Elevated cap-dependent translation initiation, driven by eIF4G activity, is a downstream effector of the TORC1/TOR nutrient-sensing pathway; hyperactive TOR signaling promotes eIF4F assembly and global protein synthesis, which is a well-established driver of aging and reduced lifespan in yeast and other organisms. Reducing eIF4G activity (or globally dampening translation initiation) mimics caloric restriction and extends chronological and replicative lifespan in yeast, consistent with the idea that the normal pro-translational function of TIF4631 opposes longevity. The molecular condensate scaffold activity of eIF4G also supports stress granule/P-body dynamics, but its primary aging-relevant role is sustaining high rates of mRNA translation that antagonize proteostasis and nutrient-sensing longevity pathways. Loss-of-proteostasis is a secondary concern, but the dominant mechanism is through deregulated nutrient sensing (TOR-eIF4F axis).
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 predicts TIF4631 as anti_longevity with good confidence (0.72). The mechanistic reasoning is sound: TIF4631 encodes eIF4G, a key translation initiation scaffold, and its pro-translational activity downstream of TOR signaling is well-established as an aging driver. Reducing translation initiation extends lifespan in yeast, making TIF4631 anti-longevity. The mechanism class of "deregulated_nutrient_sensing" is reasonable, though one could argue "translation/proteostasis" is equally or more directly relevant. The reasoning is detailed and accurate, connecting TOR signaling to eIF4F complex activity and lifespan. Minor quibble: the model could have been more specific about whether the evidence comes from replicative or chronological lifespan studies, but overall the reasoning is solid.
Raw API responses
solver
{
"reasoning": "TIF4631 encodes the yeast eIF4G homolog, a central scaffold of the eIF4F translation initiation complex that recruits the 43S pre-initiation complex to the 5' cap of mRNAs. Elevated cap-dependent translation initiation, driven by eIF4G activity, is a downstream effector of the TORC1/TOR nutrient-sensing pathway; hyperactive TOR signaling promotes eIF4F assembly and global protein synthesis, which is a well-established driver of aging and reduced lifespan in yeast and other organisms. Reducing eIF4G activity (or globally dampening translation initiation) mimics caloric restriction and extends chronological and replicative lifespan in yeast, consistent with the idea that the normal pro-translational function of TIF4631 opposes longevity. The molecular condensate scaffold activity of eIF4G also supports stress granule/P-body dynamics, but its primary aging-relevant role is sustaining high rates of mRNA translation that antagonize proteostasis and nutrient-sensing longevity pathways. Loss-of-proteostasis is a secondary concern, but the dominant mechanism is through deregulated nutrient sensing (TOR-eIF4F axis).",
"confidence": 0.72,
"key_pathways": [
"TOR-eIF4F cap-dependent translation initiation",
"TORC1 nutrient sensing",
"eIF4G scaffold assembly (eIF4E/eIF4A/eIF4G complex)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicts TIF4631 as anti_longevity with good confidence (0.72). The mechanistic reasoning is sound: TIF4631 encodes eIF4G, a key translation initiation scaffold, and its pro-translational activity downstream of TOR signaling is well-established as an aging driver. Reducing translation initiation extends lifespan in yeast, making TIF4631 anti-longevity. The mechanism class of \"deregulated_nutrient_sensing\" is reasonable, though one could argue \"translation/proteostasis\" is equally or more directly relevant. The reasoning is detailed and accurate, connecting TOR signaling to eIF4F complex activity and lifespan. Minor quibble: the model could have been more specific about whether the evidence comes from replicative or chronological lifespan studies, but overall the reasoning is solid.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}