MRPL49
S. cerevisiae
mitochondrial 54S ribosomal protein bL21m MRPL49
What the model saw
Gene: MRPL49 Organism: Saccharomyces cerevisiae Known functions: mitochondrial 54S ribosomal protein bL21m MRPL49. structural constituent of ribosome.
View unredacted entry
mitochondrial 54S ribosomal protein bL21m MRPL49. structural constituent of ribosome.
Solver output
MRPL49 encodes a structural component of the mitochondrial large (54S) ribosomal subunit (bL21m), which is essential for translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Proper mitochondrial ribosome assembly and function is required for maintaining respiratory chain integrity and efficient ATP production. Loss of mitochondrial ribosomal proteins typically impairs OXPHOS, increases reactive oxygen species, and accelerates aging-associated mitochondrial dysfunction. In yeast, intact mitochondrial translation is generally required for healthy chronological and replicative lifespan, placing this gene in a pro-longevity role through its support of mitochondrial proteostasis and bioenergetics. However, some yeast longevity studies show that partial reduction of mitochondrial translation can paradoxically extend lifespan via retrograde signaling, introducing moderate uncertainty.
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 assumed that mitochondrial ribosomal proteins are generally pro-longevity because they support OXPHOS and mitochondrial function. However, in yeast, deletion of MRPL49 (and many other mitochondrial ribosomal proteins) actually extends lifespan — making it anti_longevity (i.e., the gene normally limits lifespan, and its loss is beneficial). The model did briefly acknowledge the paradox of mitochondrial translation reduction extending lifespan via retrograde signaling, but dismissed it and still chose pro_longevity. The mechanistic reasoning was therefore also incorrect in its conclusion. The confidence of 0.62 is moderate but still led to a wrong answer.
Raw API responses
solver
{
"reasoning": "MRPL49 encodes a structural component of the mitochondrial large (54S) ribosomal subunit (bL21m), which is essential for translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Proper mitochondrial ribosome assembly and function is required for maintaining respiratory chain integrity and efficient ATP production. Loss of mitochondrial ribosomal proteins typically impairs OXPHOS, increases reactive oxygen species, and accelerates aging-associated mitochondrial dysfunction. In yeast, intact mitochondrial translation is generally required for healthy chronological and replicative lifespan, placing this gene in a pro-longevity role through its support of mitochondrial proteostasis and bioenergetics. However, some yeast longevity studies show that partial reduction of mitochondrial translation can paradoxically extend lifespan via retrograde signaling, introducing moderate uncertainty.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation",
"oxidative phosphorylation",
"mitochondrial ribosome assembly"
],
"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 assumed that mitochondrial ribosomal proteins are generally pro-longevity because they support OXPHOS and mitochondrial function. However, in yeast, deletion of MRPL49 (and many other mitochondrial ribosomal proteins) actually extends lifespan — making it anti_longevity (i.e., the gene normally limits lifespan, and its loss is beneficial). The model did briefly acknowledge the paradox of mitochondrial translation reduction extending lifespan via retrograde signaling, but dismissed it and still chose pro_longevity. The mechanistic reasoning was therefore also incorrect in its conclusion. The confidence of 0.62 is moderate but still led to a wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}