mrpl-2
C. elegans
Large ribosomal subunit protein uL2 C-terminal domain-containing protein;Ribosomal_L2_C domain-containing protein
What the model saw
Gene: mrpl-2 Organism: Caenorhabditis elegans Known functions: Large ribosomal subunit protein uL2 C-terminal domain-containing protein;Ribosomal_L2_C domain-containing protein. RNA binding. structural constituent of ribosome.
View unredacted entry
Large ribosomal subunit protein uL2 C-terminal domain-containing protein;Ribosomal_L2_C domain-containing protein. RNA binding. structural constituent of ribosome.
Solver output
mrpl-2 encodes the mitochondrial large ribosomal subunit protein uL2, which is a structural constituent of the mitochondrial ribosome (mitoribosome) responsible for translating mitochondrially-encoded proteins. Partial loss-of-function of mitoribosomal subunits in C. elegans is well-documented to activate the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1 pathway, which paradoxically extends lifespan. This phenomenon, termed mitohormesis, occurs when mild mitochondrial translation impairment triggers a compensatory stress response that improves proteostasis and metabolic efficiency. Knockdown of mrpl-2 (like other mrpl genes) reduces mitochondrial OXPHOS complex assembly, lowering ROS production and activating longevity-promoting transcriptional programs. Thus, the normal function of mrpl-2 (supporting full mitochondrial translation) is associated with a pro-longevity outcome when mildly reduced, but the gene's intact function itself supports mitochondrial homeostasis, placing it in a nuanced pro-longevity category through UPRmt signaling.
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 is internally confused: it correctly identifies that mrpl-2 knockdown can activate UPRmt and extend lifespan (which would make mrpl-2 anti_longevity — i.e., its normal function opposes longevity), but then incorrectly concludes the gene is pro_longevity. The GenAge classification of anti_longevity means that the gene's normal function works against longevity (i.e., reducing it extends life), which is exactly what the UPRmt/mitohormesis mechanism would predict. The model essentially described the correct mechanism but drew the opposite conclusion about the longevity influence classification. This is a case of right mechanistic description but wrong final answer due to misinterpretation of the pro/anti longevity framing.
Raw API responses
solver
{
"reasoning": "mrpl-2 encodes the mitochondrial large ribosomal subunit protein uL2, which is a structural constituent of the mitochondrial ribosome (mitoribosome) responsible for translating mitochondrially-encoded proteins. Partial loss-of-function of mitoribosomal subunits in C. elegans is well-documented to activate the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1 pathway, which paradoxically extends lifespan. This phenomenon, termed mitohormesis, occurs when mild mitochondrial translation impairment triggers a compensatory stress response that improves proteostasis and metabolic efficiency. Knockdown of mrpl-2 (like other mrpl genes) reduces mitochondrial OXPHOS complex assembly, lowering ROS production and activating longevity-promoting transcriptional programs. Thus, the normal function of mrpl-2 (supporting full mitochondrial translation) is associated with a pro-longevity outcome when mildly reduced, but the gene's intact function itself supports mitochondrial homeostasis, placing it in a nuanced pro-longevity category through UPRmt signaling.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial unfolded protein response (UPRmt)",
"mitochondrial translation / OXPHOS complex assembly",
"mitohormesis / ATFS-1 signaling"
],
"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 is internally confused: it correctly identifies that mrpl-2 knockdown can activate UPRmt and extend lifespan (which would make mrpl-2 anti_longevity — i.e., its normal function opposes longevity), but then incorrectly concludes the gene is pro_longevity. The GenAge classification of anti_longevity means that the gene's normal function works against longevity (i.e., reducing it extends life), which is exactly what the UPRmt/mitohormesis mechanism would predict. The model essentially described the correct mechanism but drew the opposite conclusion about the longevity influence classification. This is a case of right mechanistic description but wrong final answer due to misinterpretation of the pro/anti longevity framing.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}