lin-28
C. elegans
Protein lin-28
What the model saw
Gene: lin-28 Organism: Caenorhabditis elegans Known functions: Protein lin-28. enzyme binding. mRNA 3'-UTR binding. mRNA CDS binding. mRNA binding. nucleic acid binding. pre-miRNA binding. primary miRNA binding. zinc ion binding.
View unredacted entry
Protein lin-28. enzyme binding. mRNA 3'-UTR binding. mRNA CDS binding. mRNA binding. nucleic acid binding. pre-miRNA binding. primary miRNA binding. zinc ion binding.
Solver output
LIN-28 is a conserved RNA-binding protein that binds pre-miRNA and primary miRNA, most critically acting as a potent inhibitor of let-7 miRNA biogenesis by blocking Drosha and Dicer processing. In C. elegans, let-7 is a pro-longevity heterochronic miRNA that promotes adult fate and represses growth-promoting pathways; LIN-28 suppression of let-7 therefore maintains a juvenile, growth-promoting gene expression state. LIN-28 also binds mRNA 3'-UTRs and CDS regions to promote translation of targets including insulin/IGF-1 pathway components, which are well-established anti-longevity signals in C. elegans. Its zinc-ion binding (cold-shock domain + CCHC zinc knuckles) mediates RNA recognition central to these regulatory functions. By antagonizing let-7 and promoting nutrient/growth signaling, LIN-28 normal function opposes longevity.
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 anti_longevity for lin-28 in C. elegans. The mechanistic reasoning is excellent and well-grounded: LIN-28 is indeed a well-characterized inhibitor of let-7 miRNA biogenesis, and let-7 is a pro-longevity miRNA in C. elegans. The model correctly identifies the heterochronic pathway, the let-7/LIN-28 axis, and the potential connection to insulin/IGF-1 signaling. The mechanism class of "epigenetic_alterations" is a reasonable categorization for post-transcriptional RNA regulation, though one could argue it's more accurately "post-transcriptional regulation" — but this is a minor classification quibble. The confidence of 0.78 is appropriate given the well-established biology. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "LIN-28 is a conserved RNA-binding protein that binds pre-miRNA and primary miRNA, most critically acting as a potent inhibitor of let-7 miRNA biogenesis by blocking Drosha and Dicer processing. In C. elegans, let-7 is a pro-longevity heterochronic miRNA that promotes adult fate and represses growth-promoting pathways; LIN-28 suppression of let-7 therefore maintains a juvenile, growth-promoting gene expression state. LIN-28 also binds mRNA 3'-UTRs and CDS regions to promote translation of targets including insulin/IGF-1 pathway components, which are well-established anti-longevity signals in C. elegans. Its zinc-ion binding (cold-shock domain + CCHC zinc knuckles) mediates RNA recognition central to these regulatory functions. By antagonizing let-7 and promoting nutrient/growth signaling, LIN-28 normal function opposes longevity.",
"confidence": 0.78,
"key_pathways": [
"let-7 miRNA biogenesis inhibition",
"insulin/IGF-1 signaling (DAF-2/DAF-16 axis)",
"heterochronic pathway regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for lin-28 in C. elegans. The mechanistic reasoning is excellent and well-grounded: LIN-28 is indeed a well-characterized inhibitor of let-7 miRNA biogenesis, and let-7 is a pro-longevity miRNA in C. elegans. The model correctly identifies the heterochronic pathway, the let-7/LIN-28 axis, and the potential connection to insulin/IGF-1 signaling. The mechanism class of \"epigenetic_alterations\" is a reasonable categorization for post-transcriptional RNA regulation, though one could argue it's more accurately \"post-transcriptional regulation\" — but this is a minor classification quibble. The confidence of 0.78 is appropriate given the well-established biology. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}