mir-34
D. melanogaster
mir-34 stem loop
What the model saw
Gene: mir-34 Organism: Drosophila melanogaster Known functions: mir-34 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
View unredacted entry
mir-34 stem loop. mRNA 3'-UTR binding. mRNA base-pairing post-transcriptional repressor activity.
Solver output
mir-34 is a conserved microRNA that acts as a post-transcriptional repressor by binding mRNA 3'-UTRs and suppressing target gene expression. In Drosophila, mir-34 is strongly upregulated with age and has been shown to be required for normal aging: loss of mir-34 leads to accelerated neurodegeneration and shortened lifespan, while its expression supports brain integrity during aging. Its targets include components of the apoptosis and autophagy pathways, and it represses pro-aging transcripts, thereby maintaining tissue homeostasis. This places mir-34 in the epigenetic/post-transcriptional regulatory layer of aging control, analogous to its role in mammals where it targets SIRT1 and other longevity-associated genes. The net effect of mir-34 activity in Drosophila is neuroprotective and pro-longevity, as evidenced by the severe age-related phenotypes observed upon its loss.
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-34 in Drosophila melanogaster. The mechanistic reasoning is accurate and well-detailed: mir-34 is indeed upregulated with age, loss of mir-34 leads to accelerated neurodegeneration and shortened lifespan, and it acts as a post-transcriptional repressor via mRNA 3'-UTR binding. The classification as "epigenetic_alterations" is a reasonable categorization for miRNA-mediated post-transcriptional regulation, though one could argue it's more precisely "post-transcriptional regulation." The mention of SIRT1 targeting in mammals is a reasonable analogy. The confidence of 0.72 is appropriate given the complexity of the question. Overall, this is a high-quality, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "mir-34 is a conserved microRNA that acts as a post-transcriptional repressor by binding mRNA 3'-UTRs and suppressing target gene expression. In Drosophila, mir-34 is strongly upregulated with age and has been shown to be required for normal aging: loss of mir-34 leads to accelerated neurodegeneration and shortened lifespan, while its expression supports brain integrity during aging. Its targets include components of the apoptosis and autophagy pathways, and it represses pro-aging transcripts, thereby maintaining tissue homeostasis. This places mir-34 in the epigenetic/post-transcriptional regulatory layer of aging control, analogous to its role in mammals where it targets SIRT1 and other longevity-associated genes. The net effect of mir-34 activity in Drosophila is neuroprotective and pro-longevity, as evidenced by the severe age-related phenotypes observed upon its loss.",
"confidence": 0.72,
"key_pathways": [
"miRNA-mediated post-transcriptional gene silencing",
"neurodegeneration/neuroprotection during aging",
"apoptosis and autophagy regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for mir-34 in Drosophila melanogaster. The mechanistic reasoning is accurate and well-detailed: mir-34 is indeed upregulated with age, loss of mir-34 leads to accelerated neurodegeneration and shortened lifespan, and it acts as a post-transcriptional repressor via mRNA 3'-UTR binding. The classification as \"epigenetic_alterations\" is a reasonable categorization for miRNA-mediated post-transcriptional regulation, though one could argue it's more precisely \"post-transcriptional regulation.\" The mention of SIRT1 targeting in mammals is a reasonable analogy. The confidence of 0.72 is appropriate given the complexity of the question. Overall, this is a high-quality, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}