ISM1
S. cerevisiae
isoleucine--tRNA ligase ISM1
What the model saw
Gene: ISM1 Organism: Saccharomyces cerevisiae Known functions: isoleucine--tRNA ligase ISM1. ATP binding. aminoacyl-tRNA deacylase activity. aminoacyl-tRNA ligase activity. isoleucine-tRNA ligase activity. nucleotide binding. tRNA binding. zinc ion binding.
View unredacted entry
isoleucine--tRNA ligase ISM1. ATP binding. aminoacyl-tRNA deacylase activity. aminoacyl-tRNA ligase activity. isoleucine-tRNA ligase activity. nucleotide binding. tRNA binding. zinc ion binding.
Solver output
ISM1 encodes the mitochondrial isoleucine-tRNA synthetase (IleRS) in S. cerevisiae, responsible for charging tRNA-Ile with isoleucine specifically within the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the 8 mitochondrially-encoded proteins (components of the oxidative phosphorylation complexes). Loss of ISM1 function would impair mitochondrial translation fidelity and proteostasis, leading to defective respiratory chain assembly and mitochondrial dysfunction. The aminoacyl-tRNA deacylase activity provides an editing/proofreading function that prevents misaminoacylation, further safeguarding translational accuracy. Proper mitochondrial proteostasis and respiratory function are well-established determinants of yeast replicative and chronological lifespan, placing ISM1 in a pro-longevity role through maintenance of mitochondrial protein quality.
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 ISM1 as a mitochondrial isoleucine-tRNA synthetase is mechanistically plausible and well-articulated, but it led to the wrong conclusion. The model assumed that because ISM1 maintains mitochondrial proteostasis and respiratory function, it must be pro-longevity. However, the ground truth indicates ISM1 is anti_longevity, meaning its deletion or loss likely extends lifespan. This could be consistent with the idea that reducing mitochondrial translation (and thus OXPHOS activity) can extend lifespan through mechanisms like reduced ROS production or activation of mitochondrial stress responses (mitohormesis). The model's reasoning was coherent but reached the wrong conclusion, and the confidence of 0.72 was relatively high for an incorrect answer.
Raw API responses
solver
{
"reasoning": "ISM1 encodes the mitochondrial isoleucine-tRNA synthetase (IleRS) in S. cerevisiae, responsible for charging tRNA-Ile with isoleucine specifically within the mitochondrial compartment. Accurate aminoacylation of mitochondrial tRNAs is essential for faithful translation of the 8 mitochondrially-encoded proteins (components of the oxidative phosphorylation complexes). Loss of ISM1 function would impair mitochondrial translation fidelity and proteostasis, leading to defective respiratory chain assembly and mitochondrial dysfunction. The aminoacyl-tRNA deacylase activity provides an editing/proofreading function that prevents misaminoacylation, further safeguarding translational accuracy. Proper mitochondrial proteostasis and respiratory function are well-established determinants of yeast replicative and chronological lifespan, placing ISM1 in a pro-longevity role through maintenance of mitochondrial protein quality.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial tRNA aminoacylation",
"mitochondrial translation fidelity",
"oxidative phosphorylation complex assembly"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ISM1 as a mitochondrial isoleucine-tRNA synthetase is mechanistically plausible and well-articulated, but it led to the wrong conclusion. The model assumed that because ISM1 maintains mitochondrial proteostasis and respiratory function, it must be pro-longevity. However, the ground truth indicates ISM1 is anti_longevity, meaning its deletion or loss likely extends lifespan. This could be consistent with the idea that reducing mitochondrial translation (and thus OXPHOS activity) can extend lifespan through mechanisms like reduced ROS production or activation of mitochondrial stress responses (mitohormesis). The model's reasoning was coherent but reached the wrong conclusion, and the confidence of 0.72 was relatively high for an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}