mrpl-44
C. elegans
Large ribosomal subunit protein mL44
What the model saw
Gene: mrpl-44 Organism: Caenorhabditis elegans Known functions: Large ribosomal subunit protein mL44. double-stranded RNA binding. ribonuclease III activity.
View unredacted entry
Large ribosomal subunit protein mL44. double-stranded RNA binding. ribonuclease III activity.
Solver output
mrpl-44 encodes the mitochondrial large ribosomal subunit protein mL44, which is a core component of the mitochondrial ribosome (mitoribosome) required for translation of mitochondrially-encoded OXPHOS subunits. Its ribonuclease III activity and dsRNA binding function suggest a role in mitochondrial rRNA processing and ribosome assembly. In C. elegans, partial loss-of-function of mitoribosomal components (e.g., via RNAi) is well-documented to extend lifespan by reducing mitochondrial translation, attenuating OXPHOS activity, and triggering the mitochondrial unfolded protein response (UPRmt), a pathway strongly linked to longevity. Thus, the normal (full) function of mrpl-44 — promoting efficient mitochondrial translation — opposes longevity by sustaining high OXPHOS output and suppressing the UPRmt signal. This places mrpl-44 in the anti-longevity category, as its knockdown, not its activity, is what extends lifespan.
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 mrpl-44. The mechanistic reasoning is thorough and accurate: mrpl-44 encodes a mitochondrial large ribosomal subunit protein, and its knockdown (via RNAi) extends lifespan in C. elegans by reducing mitochondrial translation and OXPHOS activity, triggering UPRmt. The model correctly identifies that the gene's normal function opposes longevity, placing it in the anti_longevity category. The confidence level of 0.72 is appropriate given the well-established literature on mitoribosomal subunit knockdowns extending lifespan in C. elegans.
Raw API responses
solver
{
"reasoning": "mrpl-44 encodes the mitochondrial large ribosomal subunit protein mL44, which is a core component of the mitochondrial ribosome (mitoribosome) required for translation of mitochondrially-encoded OXPHOS subunits. Its ribonuclease III activity and dsRNA binding function suggest a role in mitochondrial rRNA processing and ribosome assembly. In C. elegans, partial loss-of-function of mitoribosomal components (e.g., via RNAi) is well-documented to extend lifespan by reducing mitochondrial translation, attenuating OXPHOS activity, and triggering the mitochondrial unfolded protein response (UPRmt), a pathway strongly linked to longevity. Thus, the normal (full) function of mrpl-44 — promoting efficient mitochondrial translation — opposes longevity by sustaining high OXPHOS output and suppressing the UPRmt signal. This places mrpl-44 in the anti-longevity category, as its knockdown, not its activity, is what extends lifespan.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial translation / mitoribosome assembly",
"oxidative phosphorylation (OXPHOS)",
"mitochondrial unfolded protein response (UPRmt)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for mrpl-44. The mechanistic reasoning is thorough and accurate: mrpl-44 encodes a mitochondrial large ribosomal subunit protein, and its knockdown (via RNAi) extends lifespan in C. elegans by reducing mitochondrial translation and OXPHOS activity, triggering UPRmt. The model correctly identifies that the gene's normal function opposes longevity, placing it in the anti_longevity category. The confidence level of 0.72 is appropriate given the well-established literature on mitoribosomal subunit knockdowns extending lifespan in C. elegans.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}