mrps-9
C. elegans
Small ribosomal subunit protein uS9m
What the model saw
Gene: mrps-9 Organism: Caenorhabditis elegans Known functions: Small ribosomal subunit protein uS9m. RNA binding. structural constituent of ribosome.
View unredacted entry
Small ribosomal subunit protein uS9m. RNA binding. structural constituent of ribosome.
Solver output
mrps-9 encodes the mitochondrial small ribosomal subunit protein uS9m, which is a structural component of the mitochondrial ribosome (mitoribosome) responsible for translating the 13 mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Partial loss-of-function of mitoribosomal components in C. elegans is well-documented to activate the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1/UBL-5 pathway, which paradoxically extends lifespan. This phenomenon, termed mitohormesis, occurs when mild mitochondrial translation impairment signals a compensatory stress response that improves mitochondrial quality control and proteostasis. Knockdown of mrps-9 (like other mrps genes) is predicted to reduce mitochondrial translation efficiency, triggering UPRmt activation and lifespan extension in C. elegans, consistent with findings from RNAi screens targeting mitoribosomal subunits. Thus, the normal function of mrps-9 (supporting full mitochondrial translation) is associated with a pro-longevity outcome when mildly reduced, but the gene's intact function itself supports mitochondrial homeostasis.
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 predicted "pro_longevity" but the ground truth is "anti_longevity." The model's reasoning about UPRmt and mitohormesis is a plausible general framework for mitoribosomal genes in C. elegans, but it leads to the wrong conclusion here. The model conflates the effect of knockdown (which may extend lifespan via UPRmt) with the gene's longevity influence classification. In GenAge, "anti_longevity" means the gene's normal function works against longevity — i.e., loss/reduction of the gene extends lifespan. The model actually describes this mechanism correctly (knockdown extends lifespan) but then incorrectly labels the gene as "pro_longevity." This is a logical inconsistency: if reducing mrps-9 extends lifespan, the gene is anti-longevity (its normal function shortens life). The model's final classification contradicts its own mechanistic reasoning, and it was fairly confident (0.72) in the wrong answer.
Raw API responses
solver
{
"reasoning": "mrps-9 encodes the mitochondrial small ribosomal subunit protein uS9m, which is a structural component of the mitochondrial ribosome (mitoribosome) responsible for translating the 13 mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Partial loss-of-function of mitoribosomal components in C. elegans is well-documented to activate the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1/UBL-5 pathway, which paradoxically extends lifespan. This phenomenon, termed mitohormesis, occurs when mild mitochondrial translation impairment signals a compensatory stress response that improves mitochondrial quality control and proteostasis. Knockdown of mrps-9 (like other mrps genes) is predicted to reduce mitochondrial translation efficiency, triggering UPRmt activation and lifespan extension in C. elegans, consistent with findings from RNAi screens targeting mitoribosomal subunits. Thus, the normal function of mrps-9 (supporting full mitochondrial translation) is associated with a pro-longevity outcome when mildly reduced, but the gene's intact function itself supports mitochondrial homeostasis.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial unfolded protein response (UPRmt)",
"mitochondrial translation / oxidative phosphorylation",
"mitohormesis signaling via ATFS-1"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning about UPRmt and mitohormesis is a plausible general framework for mitoribosomal genes in C. elegans, but it leads to the wrong conclusion here. The model conflates the effect of knockdown (which may extend lifespan via UPRmt) with the gene's longevity influence classification. In GenAge, \"anti_longevity\" means the gene's normal function works against longevity — i.e., loss/reduction of the gene extends lifespan. The model actually describes this mechanism correctly (knockdown extends lifespan) but then incorrectly labels the gene as \"pro_longevity.\" This is a logical inconsistency: if reducing mrps-9 extends lifespan, the gene is anti-longevity (its normal function shortens life). The model's final classification contradicts its own mechanistic reasoning, and it was fairly confident (0.72) in the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}