rle-1
C. elegans
Regulation of longevity by E3 ubiquitin-protein ligase
What the model saw
Gene: rle-1 Organism: Caenorhabditis elegans Known functions: Regulation of [REDACTED] by E3 ubiquitin-protein ligase. RNA stem-loop binding. double-stranded RNA binding. mRNA binding. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
View unredacted entry
Regulation of longevity by E3 ubiquitin-protein ligase. RNA stem-loop binding. double-stranded RNA binding. mRNA binding. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity.
Solver output
rle-1 encodes an E3 ubiquitin-protein ligase in C. elegans that has been shown to ubiquitinate and target DAF-16 (the FOXO transcription factor) for degradation. The redacted target is almost certainly DAF-16, given rle-1's known role in the insulin/IGF-1 signaling (IIS) pathway. However, rle-1 loss-of-function extends lifespan by relieving DAF-16 degradation, meaning the normal function of rle-1 is to suppress DAF-16 activity and thus oppose longevity. Wait — if rle-1 normally degrades DAF-16, its normal function is anti-longevity. Re-evaluating: rle-1 promotes ubiquitination and degradation of DAF-16/FOXO, which is the master pro-longevity transcription factor downstream of reduced IIS signaling. By targeting DAF-16 for proteasomal degradation, rle-1's normal activity suppresses the transcriptional program that extends lifespan, making rle-1 itself anti-longevity in function.
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 identified the mechanism: rle-1 encodes an E3 ubiquitin ligase that targets DAF-16/FOXO for degradation, suppressing the pro-longevity transcriptional program. This makes rle-1 anti-longevity, which is the ground truth. However, the model's final answer was "pro_longevity" despite its own reasoning explicitly concluding that rle-1 is anti-longevity. The model visibly corrected itself mid-reasoning ("Re-evaluating: rle-1 promotes ubiquitination and degradation of DAF-16/FOXO...making rle-1 itself anti-longevity in function") but then submitted the wrong label "pro_longevity" with 0.72 confidence. This is a clear failure where the final answer contradicts the model's own stated conclusion. The mechanism reasoning was correct, but the final classification was wrong.
Raw API responses
solver
{
"reasoning": "rle-1 encodes an E3 ubiquitin-protein ligase in C. elegans that has been shown to ubiquitinate and target DAF-16 (the FOXO transcription factor) for degradation. The redacted target is almost certainly DAF-16, given rle-1's known role in the insulin/IGF-1 signaling (IIS) pathway. However, rle-1 loss-of-function extends lifespan by relieving DAF-16 degradation, meaning the normal function of rle-1 is to suppress DAF-16 activity and thus oppose longevity. Wait — if rle-1 normally degrades DAF-16, its normal function is anti-longevity. Re-evaluating: rle-1 promotes ubiquitination and degradation of DAF-16/FOXO, which is the master pro-longevity transcription factor downstream of reduced IIS signaling. By targeting DAF-16 for proteasomal degradation, rle-1's normal activity suppresses the transcriptional program that extends lifespan, making rle-1 itself anti-longevity in function.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"DAF-16/FOXO ubiquitin-mediated degradation",
"ubiquitin-proteasome system"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanism: rle-1 encodes an E3 ubiquitin ligase that targets DAF-16/FOXO for degradation, suppressing the pro-longevity transcriptional program. This makes rle-1 anti-longevity, which is the ground truth. However, the model's final answer was \"pro_longevity\" despite its own reasoning explicitly concluding that rle-1 is anti-longevity. The model visibly corrected itself mid-reasoning (\"Re-evaluating: rle-1 promotes ubiquitination and degradation of DAF-16/FOXO...making rle-1 itself anti-longevity in function\") but then submitted the wrong label \"pro_longevity\" with 0.72 confidence. This is a clear failure where the final answer contradicts the model's own stated conclusion. The mechanism reasoning was correct, but the final classification was wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}