nobh-1
C. elegans
RNA-binding protein NOB1
What the model saw
Gene: nobh-1 Organism: Caenorhabditis elegans Known functions: RNA-binding protein NOB1. RNA endonuclease activity. metal ion binding.
View unredacted entry
RNA-binding protein NOB1. RNA endonuclease activity. metal ion binding.
Solver output
NOB1 (Pin domain-containing RNA endonuclease) is a conserved factor essential for the final maturation step of the 20S pre-rRNA into the mature 18S rRNA, a process required for 40S ribosomal subunit biogenesis. Ribosome biogenesis is a major anabolic output of TOR (mTORC1) signaling; elevated ribosome production is a hallmark of pro-growth, pro-aging states. In C. elegans, reduced ribosomal biogenesis and translation capacity (e.g., via TOR inhibition or ribosomal protein knockdown) consistently extends lifespan. Because nobh-1 encodes the endonuclease that completes 18S rRNA processing and thus enables 40S subunit assembly, its normal function promotes ribosome production and translational capacity downstream of nutrient/TOR signaling. Loss of nobh-1 function would be expected to reduce ribosome output and extend lifespan, placing its normal activity in the anti-longevity category. The metal ion binding activity is consistent with the PIN-domain zinc-coordinating active site required for this endonucleolytic cleavage.
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 nobh-1. The mechanistic reasoning is sound and well-articulated: NOB1 is an RNA endonuclease involved in 18S rRNA maturation and 40S ribosomal subunit biogenesis, and the model correctly connects ribosome biogenesis to TOR/nutrient sensing pathways where reduced ribosomal output extends lifespan in C. elegans. The mechanism_class of "deregulated_nutrient_sensing" is a reasonable (if slightly imprecise) categorization — the more direct mechanism is ribosome biogenesis/translation, but TOR signaling is upstream and closely linked. The confidence of 0.62 is appropriately moderate given the indirect inference. Overall, this is a well-reasoned correct prediction.
Raw API responses
solver
{
"reasoning": "NOB1 (Pin domain-containing RNA endonuclease) is a conserved factor essential for the final maturation step of the 20S pre-rRNA into the mature 18S rRNA, a process required for 40S ribosomal subunit biogenesis. Ribosome biogenesis is a major anabolic output of TOR (mTORC1) signaling; elevated ribosome production is a hallmark of pro-growth, pro-aging states. In C. elegans, reduced ribosomal biogenesis and translation capacity (e.g., via TOR inhibition or ribosomal protein knockdown) consistently extends lifespan. Because nobh-1 encodes the endonuclease that completes 18S rRNA processing and thus enables 40S subunit assembly, its normal function promotes ribosome production and translational capacity downstream of nutrient/TOR signaling. Loss of nobh-1 function would be expected to reduce ribosome output and extend lifespan, placing its normal activity in the anti-longevity category. The metal ion binding activity is consistent with the PIN-domain zinc-coordinating active site required for this endonucleolytic cleavage.",
"confidence": 0.62,
"key_pathways": [
"rRNA processing / 18S rRNA maturation",
"40S ribosomal subunit biogenesis",
"TOR-dependent nutrient sensing and translation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nobh-1. The mechanistic reasoning is sound and well-articulated: NOB1 is an RNA endonuclease involved in 18S rRNA maturation and 40S ribosomal subunit biogenesis, and the model correctly connects ribosome biogenesis to TOR/nutrient sensing pathways where reduced ribosomal output extends lifespan in C. elegans. The mechanism_class of \"deregulated_nutrient_sensing\" is a reasonable (if slightly imprecise) categorization — the more direct mechanism is ribosome biogenesis/translation, but TOR signaling is upstream and closely linked. The confidence of 0.62 is appropriately moderate given the indirect inference. Overall, this is a well-reasoned correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}