mir-277
D. melanogaster
mir-277 stem loop
What the model saw
Gene: mir-277 Organism: Drosophila melanogaster Known functions: mir-277 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
View unredacted entry
mir-277 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
Solver output
mir-277 is a microRNA in Drosophila that binds mRNA 3'-UTRs and acts as a post-transcriptional repressor via base-pairing. In Drosophila, mir-277 has been specifically shown to target branched-chain amino acid (BCAA) catabolic enzymes, thereby modulating amino acid catabolism and nutrient sensing. By repressing key metabolic targets, mir-277 can influence the TOR (Target of Rapamycin) nutrient-sensing pathway, which is a central regulator of aging and longevity. Downregulation of TOR signaling through reduced amino acid availability is a well-established pro-longevity mechanism in Drosophila. The miRNA's role in dampening BCAA catabolism and thus modulating nutrient-sensing flux places it within the deregulated nutrient-sensing hallmark of aging, with a net pro-longevity effect when functioning normally to buffer excessive TOR activation.
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 mechanistic reasoning about mir-277 targeting BCAA catabolic enzymes and modulating TOR signaling is partially grounded in real biology (mir-277 does target BCAA catabolism genes), but the model incorrectly inferred the direction of longevity effect. In reality, mir-277 overexpression or normal activity promotes aging (anti_longevity), likely because repressing BCAA catabolism leads to accumulation of BCAAs that activate TOR signaling, which shortens lifespan. The model inverted the logic — it argued that mir-277 dampens TOR activation, when in fact repressing BCAA catabolism enzymes would increase BCAA levels and thus activate TOR, which is pro-aging. The model's confidence of 0.55 is relatively low but still committed to the wrong answer. The mechanistic reasoning contains a logical error in the direction of the effect.
Raw API responses
solver
{
"reasoning": "mir-277 is a microRNA in Drosophila that binds mRNA 3'-UTRs and acts as a post-transcriptional repressor via base-pairing. In Drosophila, mir-277 has been specifically shown to target branched-chain amino acid (BCAA) catabolic enzymes, thereby modulating amino acid catabolism and nutrient sensing. By repressing key metabolic targets, mir-277 can influence the TOR (Target of Rapamycin) nutrient-sensing pathway, which is a central regulator of aging and longevity. Downregulation of TOR signaling through reduced amino acid availability is a well-established pro-longevity mechanism in Drosophila. The miRNA's role in dampening BCAA catabolism and thus modulating nutrient-sensing flux places it within the deregulated nutrient-sensing hallmark of aging, with a net pro-longevity effect when functioning normally to buffer excessive TOR activation.",
"confidence": 0.55,
"key_pathways": [
"TOR/nutrient sensing pathway",
"branched-chain amino acid catabolism",
"mRNA 3'-UTR post-transcriptional regulation"
],
"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 mechanistic reasoning about mir-277 targeting BCAA catabolic enzymes and modulating TOR signaling is partially grounded in real biology (mir-277 does target BCAA catabolism genes), but the model incorrectly inferred the direction of longevity effect. In reality, mir-277 overexpression or normal activity promotes aging (anti_longevity), likely because repressing BCAA catabolism leads to accumulation of BCAAs that activate TOR signaling, which shortens lifespan. The model inverted the logic — it argued that mir-277 dampens TOR activation, when in fact repressing BCAA catabolism enzymes would increase BCAA levels and thus activate TOR, which is pro-aging. The model's confidence of 0.55 is relatively low but still committed to the wrong answer. The mechanistic reasoning contains a logical error in the direction of the effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}