TRM9
S. cerevisiae
tRNA (carboxymethyluridine(34)-5-O)-methyltransferase
What the model saw
Gene: TRM9 Organism: Saccharomyces cerevisiae Known functions: tRNA (carboxymethyluridine(34)-5-O)-methyltransferase. S-adenosylmethionine-dependent methyltransferase activity. protein binding. tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity. tRNA (uridine) methyltransferase activity. tRNA binding. tRNA methyltransferase activity.
View unredacted entry
tRNA (carboxymethyluridine(34)-5-O)-methyltransferase. S-adenosylmethionine-dependent methyltransferase activity. protein binding. tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity. tRNA (uridine) methyltransferase activity. tRNA binding. tRNA methyltransferase activity.
Solver output
TRM9 encodes a tRNA methyltransferase that catalyzes the 5-methoxycarbonylmethyl (mcm5) modification at the wobble uridine (U34) of specific tRNAs, using S-adenosylmethionine as methyl donor. This wobble base modification is critical for efficient and accurate decoding of AGA and GAA codons, which are enriched in mRNAs encoding stress-response and DNA damage repair proteins. Loss of TRM9 impairs translational fidelity and efficiency of these codon-biased transcripts, reducing the capacity to mount proper responses to genotoxic and proteotoxic stress. In yeast, trm9 mutants show hypersensitivity to DNA-damaging agents and oxidative stress, conditions that accelerate aging. By ensuring accurate translation of stress-response proteins, TRM9 supports proteostasis and genome maintenance, both of which are central to longevity.
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 TRM9 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is mechanistically plausible in isolation (TRM9 supports stress response via tRNA modification), but it reaches the wrong conclusion. An anti_longevity designation means that TRM9 deletion or loss actually extends lifespan, suggesting TRM9 activity normally limits longevity. The model's reasoning about TRM9 supporting proteostasis and stress response would predict pro_longevity, which is the opposite of what is observed. The model's mechanistic description of TRM9's biochemical function (mcm5U34 modification, codon-biased translation) is accurate, but the interpretation of how this affects longevity is incorrect. The model had moderate confidence (0.62) but still got the direction wrong.
Raw API responses
solver
{
"reasoning": "TRM9 encodes a tRNA methyltransferase that catalyzes the 5-methoxycarbonylmethyl (mcm5) modification at the wobble uridine (U34) of specific tRNAs, using S-adenosylmethionine as methyl donor. This wobble base modification is critical for efficient and accurate decoding of AGA and GAA codons, which are enriched in mRNAs encoding stress-response and DNA damage repair proteins. Loss of TRM9 impairs translational fidelity and efficiency of these codon-biased transcripts, reducing the capacity to mount proper responses to genotoxic and proteotoxic stress. In yeast, trm9 mutants show hypersensitivity to DNA-damaging agents and oxidative stress, conditions that accelerate aging. By ensuring accurate translation of stress-response proteins, TRM9 supports proteostasis and genome maintenance, both of which are central to longevity.",
"confidence": 0.62,
"key_pathways": [
"tRNA wobble uridine modification (mcm5U34)",
"translational fidelity and codon-biased translation of stress-response genes",
"DNA damage response via accurate translation of repair factors"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted TRM9 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is mechanistically plausible in isolation (TRM9 supports stress response via tRNA modification), but it reaches the wrong conclusion. An anti_longevity designation means that TRM9 deletion or loss actually extends lifespan, suggesting TRM9 activity normally limits longevity. The model's reasoning about TRM9 supporting proteostasis and stress response would predict pro_longevity, which is the opposite of what is observed. The model's mechanistic description of TRM9's biochemical function (mcm5U34 modification, codon-biased translation) is accurate, but the interpretation of how this affects longevity is incorrect. The model had moderate confidence (0.62) but still got the direction wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}