smn-1
C. elegans
Tudor domain-containing protein
What the model saw
Gene: smn-1 Organism: Caenorhabditis elegans Known functions: Tudor domain-containing protein. protein binding.
View unredacted entry
Tudor domain-containing protein. protein binding.
Solver output
SMN-1 is the C. elegans ortholog of human Survival of Motor Neuron (SMN), a Tudor domain-containing protein essential for the assembly of small nuclear ribonucleoproteins (snRNPs) via its Tudor domain-mediated recognition of symmetrically dimethylated arginine (sDMA) on Sm proteins. Proper snRNP biogenesis is required for pre-mRNA splicing fidelity; loss of SMN-1 in C. elegans leads to widespread splicing defects that compromise proteostasis and organismal fitness. In C. elegans, smn-1 loss-of-function reduces lifespan and causes motor dysfunction, consistent with a pro-longevity role for the wild-type gene. The Tudor domain-mediated protein–protein interactions are central to RNA processing quality control, linking this gene to the maintenance of proteostasis through accurate gene expression. This places smn-1 within the loss-of-proteostasis hallmark, as disrupted RNA processing leads to aberrant protein production and proteotoxic stress.
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 predicts pro_longevity for smn-1 in C. elegans. The mechanistic reasoning is solid and well-grounded: SMN-1 is indeed the C. elegans ortholog of human SMN, it contains a Tudor domain, and it functions in snRNP biogenesis and pre-mRNA splicing. The claim that smn-1 loss-of-function reduces lifespan in C. elegans is consistent with published literature. The classification of the mechanism as "loss_of_proteostasis" is a reasonable interpretation, though one could argue RNA processing/splicing fidelity is more directly a gene expression/RNA processing issue rather than proteostasis per se. The confidence of 0.62 is appropriately moderate. Overall a strong, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "SMN-1 is the C. elegans ortholog of human Survival of Motor Neuron (SMN), a Tudor domain-containing protein essential for the assembly of small nuclear ribonucleoproteins (snRNPs) via its Tudor domain-mediated recognition of symmetrically dimethylated arginine (sDMA) on Sm proteins. Proper snRNP biogenesis is required for pre-mRNA splicing fidelity; loss of SMN-1 in C. elegans leads to widespread splicing defects that compromise proteostasis and organismal fitness. In C. elegans, smn-1 loss-of-function reduces lifespan and causes motor dysfunction, consistent with a pro-longevity role for the wild-type gene. The Tudor domain-mediated protein–protein interactions are central to RNA processing quality control, linking this gene to the maintenance of proteostasis through accurate gene expression. This places smn-1 within the loss-of-proteostasis hallmark, as disrupted RNA processing leads to aberrant protein production and proteotoxic stress.",
"confidence": 0.62,
"key_pathways": [
"snRNP biogenesis and pre-mRNA splicing",
"Tudor domain-mediated Sm protein recognition",
"RNA processing quality control"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicts pro_longevity for smn-1 in C. elegans. The mechanistic reasoning is solid and well-grounded: SMN-1 is indeed the C. elegans ortholog of human SMN, it contains a Tudor domain, and it functions in snRNP biogenesis and pre-mRNA splicing. The claim that smn-1 loss-of-function reduces lifespan in C. elegans is consistent with published literature. The classification of the mechanism as \"loss_of_proteostasis\" is a reasonable interpretation, though one could argue RNA processing/splicing fidelity is more directly a gene expression/RNA processing issue rather than proteostasis per se. The confidence of 0.62 is appropriately moderate. Overall a strong, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}