nsun-5
C. elegans
26S rRNA (cytosine-C(5))-methyltransferase nsun-5
What the model saw
Gene: nsun-5 Organism: Caenorhabditis elegans Known functions: 26S rRNA (cytosine-C(5))-methyltransferase nsun-5. RNA methyltransferase activity. methyltransferase activity. rRNA (cytosine-C5-)-methyltransferase activity.
View unredacted entry
26S rRNA (cytosine-C(5))-methyltransferase nsun-5. RNA methyltransferase activity. methyltransferase activity. rRNA (cytosine-C5-)-methyltransferase activity.
Solver output
NSUN-5 is a conserved RNA methyltransferase that installs a C5-methylcytosine (m5C) modification on 26S rRNA (equivalent to 28S rRNA in mammals) at a specific position in the large ribosomal subunit. This rRNA methylation modulates ribosome function and translational fidelity. In C. elegans, loss-of-function of nsun-5 has been shown to extend lifespan, indicating that its normal activity is anti-longevity. The mechanism involves altered ribosome activity and translation rates: reduced rRNA methylation by nsun-5 dampens overall translational output, which mimics aspects of dietary restriction and reduced mTOR/nutrient-sensing signaling, ultimately improving proteostasis and stress resistance. This places nsun-5 at the intersection of ribosome biogenesis, translational control, and proteostasis maintenance.
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 nsun-5 in C. elegans. The mechanistic reasoning is accurate and detailed: NSUN-5 is indeed an rRNA methyltransferase that installs m5C modifications on 26S rRNA, and its loss-of-function extends lifespan in C. elegans. The model correctly identifies the mechanism involving altered translational output and its connection to dietary restriction-like effects. The mechanism class of "loss_of_proteostasis" is a reasonable framing, though the primary mechanism is more specifically about translational control via rRNA methylation. The reasoning about reduced rRNA methylation dampening translational output and improving stress resistance is well-supported by the literature. Confidence of 0.72 is appropriate given the specificity of the claim.
Raw API responses
solver
{
"reasoning": "NSUN-5 is a conserved RNA methyltransferase that installs a C5-methylcytosine (m5C) modification on 26S rRNA (equivalent to 28S rRNA in mammals) at a specific position in the large ribosomal subunit. This rRNA methylation modulates ribosome function and translational fidelity. In C. elegans, loss-of-function of nsun-5 has been shown to extend lifespan, indicating that its normal activity is anti-longevity. The mechanism involves altered ribosome activity and translation rates: reduced rRNA methylation by nsun-5 dampens overall translational output, which mimics aspects of dietary restriction and reduced mTOR/nutrient-sensing signaling, ultimately improving proteostasis and stress resistance. This places nsun-5 at the intersection of ribosome biogenesis, translational control, and proteostasis maintenance.",
"confidence": 0.72,
"key_pathways": [
"rRNA m5C methylation",
"ribosome function and translational fidelity",
"proteostasis and stress response"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nsun-5 in C. elegans. The mechanistic reasoning is accurate and detailed: NSUN-5 is indeed an rRNA methyltransferase that installs m5C modifications on 26S rRNA, and its loss-of-function extends lifespan in C. elegans. The model correctly identifies the mechanism involving altered translational output and its connection to dietary restriction-like effects. The mechanism class of \"loss_of_proteostasis\" is a reasonable framing, though the primary mechanism is more specifically about translational control via rRNA methylation. The reasoning about reduced rRNA methylation dampening translational output and improving stress resistance is well-supported by the literature. Confidence of 0.72 is appropriate given the specificity of the claim.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}