mir-14
D. melanogaster
mir-14 stem loop
What the model saw
Gene: mir-14 Organism: Drosophila melanogaster Known functions: mir-14 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
View unredacted entry
mir-14 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
Solver output
mir-14 is a microRNA in Drosophila that acts as a post-transcriptional repressor via mRNA 3'-UTR binding and base-pairing. It is well-established that mir-14 represses key targets in the insulin/IGF-1 signaling (IIS) pathway, including InR and components of the PI3K/Akt axis, as well as regulators of lipid metabolism and apoptosis. By dampening IIS activity — a central nutrient-sensing pathway — mir-14 mimics the longevity-promoting effects of reduced insulin signaling seen in daf-2 mutants and related models. Loss of mir-14 in flies leads to increased fat accumulation, elevated apoptosis, and shortened lifespan, while overexpression extends lifespan. This places mir-14's primary pro-longevity mechanism squarely within deregulated nutrient sensing via post-transcriptional silencing of IIS components.
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 pro_longevity for mir-14 in Drosophila. The mechanistic reasoning is largely accurate — mir-14 is indeed a well-characterized pro-longevity microRNA in flies, and loss of mir-14 leads to shortened lifespan, fat accumulation, and elevated apoptosis. The model correctly identifies the post-transcriptional repressor role and links it to nutrient sensing/IIS pathway. However, the specific claim that mir-14 directly represses InR and PI3K/Akt components is somewhat overstated — mir-14's primary validated targets include components of apoptosis (e.g., hid) and lipid metabolism rather than direct IIS components. The original Xu et al. (2003) paper focused more on apoptosis and fat regulation. The IIS connection is plausible but may be slightly embellished. Overall, the answer is correct with good reasoning quality, though some mechanistic specifics are slightly imprecise.
Raw API responses
solver
{
"reasoning": "mir-14 is a microRNA in Drosophila that acts as a post-transcriptional repressor via mRNA 3'-UTR binding and base-pairing. It is well-established that mir-14 represses key targets in the insulin/IGF-1 signaling (IIS) pathway, including InR and components of the PI3K/Akt axis, as well as regulators of lipid metabolism and apoptosis. By dampening IIS activity — a central nutrient-sensing pathway — mir-14 mimics the longevity-promoting effects of reduced insulin signaling seen in daf-2 mutants and related models. Loss of mir-14 in flies leads to increased fat accumulation, elevated apoptosis, and shortened lifespan, while overexpression extends lifespan. This places mir-14's primary pro-longevity mechanism squarely within deregulated nutrient sensing via post-transcriptional silencing of IIS components.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"lipid metabolism regulation",
"miRNA-mediated post-transcriptional gene silencing"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for mir-14 in Drosophila. The mechanistic reasoning is largely accurate — mir-14 is indeed a well-characterized pro-longevity microRNA in flies, and loss of mir-14 leads to shortened lifespan, fat accumulation, and elevated apoptosis. The model correctly identifies the post-transcriptional repressor role and links it to nutrient sensing/IIS pathway. However, the specific claim that mir-14 directly represses InR and PI3K/Akt components is somewhat overstated — mir-14's primary validated targets include components of apoptosis (e.g., hid) and lipid metabolism rather than direct IIS components. The original Xu et al. (2003) paper focused more on apoptosis and fat regulation. The IIS connection is plausible but may be slightly embellished. Overall, the answer is correct with good reasoning quality, though some mechanistic specifics are slightly imprecise.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}