mrpl-47
C. elegans
Large ribosomal subunit protein uL29m
What the model saw
Gene: mrpl-47 Organism: Caenorhabditis elegans Known functions: Large ribosomal subunit protein uL29m. structural constituent of ribosome.
View unredacted entry
Large ribosomal subunit protein uL29m. structural constituent of ribosome.
Solver output
mrpl-47 encodes the mitochondrial large ribosomal subunit protein uL29m, which is a structural component of the mitochondrial ribosome (mitoribosome). Paradoxically, in C. elegans, partial loss-of-function of mitoribosomal subunits — including mrpl genes — activates the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1 pathway, which is a well-established pro-longevity signal. Knockdown of mitoribosomal proteins reduces mitochondrial translation efficiency, triggering a hormetic mitochondrial stress response that extends lifespan. This places mrpl-47 in the category where its normal function (supporting full mitochondrial translation) is actually anti-longevity, but since the question asks about the gene's normal function influence on longevity, reduced mitoribosomal activity (loss of mrpl-47 function) is pro-longevity. However, the normal function of mrpl-47 — maintaining robust mitochondrial protein synthesis — supports mitochondrial homeostasis, and its complete absence is detrimental. The net effect of the normal gene function is to sustain mitochondrial integrity, but the literature in C. elegans consistently shows that partial reduction of MRPL genes extends lifespan through UPRmt activation, suggesting the gene's full activity is mildly anti-longevity in this context.
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 ultimately predicted "pro_longevity" but the ground truth is "anti_longevity." Interestingly, the model's reasoning actually correctly identifies the anti-longevity mechanism — that the normal function of mrpl-47 (supporting full mitochondrial translation) is anti-longevity, and that loss-of-function extends lifespan via UPRmt. However, the model then contradicted itself by outputting "pro_longevity" as the final answer, apparently confusing the effect of loss-of-function with the gene's longevity influence classification. The mechanistic understanding is largely correct (mitoribosomal subunit knockdown extends lifespan via UPRmt), but the final answer is wrong. This is a case where the model reasoned its way to the correct mechanism but then selected the wrong label — essentially the inverse of "right answer wrong reasoning."
Raw API responses
solver
{
"reasoning": "mrpl-47 encodes the mitochondrial large ribosomal subunit protein uL29m, which is a structural component of the mitochondrial ribosome (mitoribosome). Paradoxically, in C. elegans, partial loss-of-function of mitoribosomal subunits — including mrpl genes — activates the mitochondrial unfolded protein response (UPRmt) via the ATFS-1/DVE-1 pathway, which is a well-established pro-longevity signal. Knockdown of mitoribosomal proteins reduces mitochondrial translation efficiency, triggering a hormetic mitochondrial stress response that extends lifespan. This places mrpl-47 in the category where its normal function (supporting full mitochondrial translation) is actually anti-longevity, but since the question asks about the gene's normal function influence on longevity, reduced mitoribosomal activity (loss of mrpl-47 function) is pro-longevity. However, the normal function of mrpl-47 — maintaining robust mitochondrial protein synthesis — supports mitochondrial homeostasis, and its complete absence is detrimental. The net effect of the normal gene function is to sustain mitochondrial integrity, but the literature in C. elegans consistently shows that partial reduction of MRPL genes extends lifespan through UPRmt activation, suggesting the gene's full activity is mildly anti-longevity in this context.",
"confidence": 0.65,
"key_pathways": [
"mitochondrial ribosome assembly and translation",
"mitochondrial unfolded protein response (UPRmt / ATFS-1)",
"mitochondrial dysfunction hormesis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model ultimately predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Interestingly, the model's reasoning actually correctly identifies the anti-longevity mechanism — that the normal function of mrpl-47 (supporting full mitochondrial translation) is anti-longevity, and that loss-of-function extends lifespan via UPRmt. However, the model then contradicted itself by outputting \"pro_longevity\" as the final answer, apparently confusing the effect of loss-of-function with the gene's longevity influence classification. The mechanistic understanding is largely correct (mitoribosomal subunit knockdown extends lifespan via UPRmt), but the final answer is wrong. This is a case where the model reasoned its way to the correct mechanism but then selected the wrong label — essentially the inverse of \"right answer wrong reasoning.\"",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}