eif-1
C. elegans
SUI1 domain-containing protein
What the model saw
Gene: eif-1 Organism: Caenorhabditis elegans Known functions: SUI1 domain-containing protein. RNA binding. ribosomal small subunit binding. translation initiation factor activity.
View unredacted entry
SUI1 domain-containing protein. RNA binding. ribosomal small subunit binding. translation initiation factor activity.
Solver output
eif-1 encodes a eukaryotic translation initiation factor (eIF1/SUI1) that binds the 43S pre-initiation complex on the ribosomal small subunit and promotes accurate AUG start codon selection during cap-dependent translation initiation. Reduced global translation rate is a well-established pro-longevity intervention in C. elegans, operating downstream of nutrient-sensing pathways (TOR/IIS), where partial inhibition of translation initiation machinery extends lifespan. eIF1 specifically ensures fidelity of start codon recognition; loss or reduction of eif-1 function would be expected to reduce overall translational output or alter translational fidelity, mimicking the beneficial effects of translation attenuation seen with other initiation factor knockdowns (e.g., ifg-1/eIF4G). However, since the normal function of eif-1 is to promote translation initiation, its wild-type activity supports robust protein synthesis, which is associated with faster aging under nutrient-replete conditions. Thus, the normal (pro-translation) function of eif-1 is more aligned with an anti-longevity role, but partial reduction of eIF1 activity is known to extend lifespan, placing the gene's normal function in tension with longevity. Given that translation initiation factors as a class are generally considered to oppose longevity when active (their inhibition extends lifespan via TOR-like mechanisms), eif-1's normal function is cautiously predicted as pro-longevity only if it maintains proteostasis through accurate translation; however, the dominant paradigm places active translation initiation as a driver of 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is internally contradictory and ultimately lands on the wrong answer. The model correctly identifies that translation initiation factors, when active, are generally anti-longevity (their inhibition extends lifespan), but then confusingly concludes "pro_longevity" despite acknowledging the dominant paradigm places active translation initiation as a driver of aging. The model essentially argued itself into the correct mechanistic understanding (eif-1 promotes translation → promotes aging → anti_longevity) but then output the wrong label. The mechanism class of "deregulated_nutrient_sensing" is also not the most precise description - it's more directly about translational control. The reasoning quality is poor because the model contradicts itself and arrives at the wrong final answer despite having the right mechanistic intuition at several points in the reasoning.
Raw API responses
solver
{
"reasoning": "eif-1 encodes a eukaryotic translation initiation factor (eIF1/SUI1) that binds the 43S pre-initiation complex on the ribosomal small subunit and promotes accurate AUG start codon selection during cap-dependent translation initiation. Reduced global translation rate is a well-established pro-longevity intervention in C. elegans, operating downstream of nutrient-sensing pathways (TOR/IIS), where partial inhibition of translation initiation machinery extends lifespan. eIF1 specifically ensures fidelity of start codon recognition; loss or reduction of eif-1 function would be expected to reduce overall translational output or alter translational fidelity, mimicking the beneficial effects of translation attenuation seen with other initiation factor knockdowns (e.g., ifg-1/eIF4G). However, since the normal function of eif-1 is to promote translation initiation, its wild-type activity supports robust protein synthesis, which is associated with faster aging under nutrient-replete conditions. Thus, the normal (pro-translation) function of eif-1 is more aligned with an anti-longevity role, but partial reduction of eIF1 activity is known to extend lifespan, placing the gene's normal function in tension with longevity. Given that translation initiation factors as a class are generally considered to oppose longevity when active (their inhibition extends lifespan via TOR-like mechanisms), eif-1's normal function is cautiously predicted as pro-longevity only if it maintains proteostasis through accurate translation; however, the dominant paradigm places active translation initiation as a driver of aging.",
"confidence": 0.62,
"key_pathways": [
"mTOR/TOR signaling and translational control",
"43S pre-initiation complex assembly and AUG selection",
"cap-dependent translation initiation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is internally contradictory and ultimately lands on the wrong answer. The model correctly identifies that translation initiation factors, when active, are generally anti-longevity (their inhibition extends lifespan), but then confusingly concludes \"pro_longevity\" despite acknowledging the dominant paradigm places active translation initiation as a driver of aging. The model essentially argued itself into the correct mechanistic understanding (eif-1 promotes translation → promotes aging → anti_longevity) but then output the wrong label. The mechanism class of \"deregulated_nutrient_sensing\" is also not the most precise description - it's more directly about translational control. The reasoning quality is poor because the model contradicts itself and arrives at the wrong final answer despite having the right mechanistic intuition at several points in the reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}