TIS11
S. cerevisiae
Tis11p
What the model saw
Gene: TIS11 Organism: Saccharomyces cerevisiae Known functions: Tis11p. mRNA binding. metal ion binding. translation repressor activity. zinc ion binding.
View unredacted entry
Tis11p. mRNA binding. metal ion binding. translation repressor activity. zinc ion binding.
Solver output
TIS11 (Tis11p) is a zinc finger RNA-binding protein that functions as an mRNA-binding translation repressor, homologous to the mammalian TTP (tristetraprolin) family. By binding to AU-rich elements (AREs) in target mRNAs and repressing their translation, TIS11 can dampen the expression of potentially harmful or pro-aging transcripts. Translation repression is a key mechanism for maintaining proteostasis by limiting the production of misfolded or aggregation-prone proteins. Additionally, global translational repression is a well-established pro-longevity mechanism in yeast and other organisms (e.g., via TOR pathway inhibition), and ARE-mediated mRNA regulation can suppress inflammatory or stress-response transcripts. The zinc ion binding activity is structural, supporting the CCCH-type zinc finger domains required for mRNA recognition. Overall, the translation repressor function aligns with pro-longevity roles seen for other translational regulators in yeast.
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 constructed a plausible-sounding but incorrect mechanistic argument, reasoning that translation repression generally promotes longevity. In reality, TIS11 in yeast is anti-longevity, meaning its deletion or loss extends lifespan. The model's reasoning about translational repression being pro-longevity is a general heuristic that doesn't apply here. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer. The mechanism proposed (proteostasis via translational control) is also incorrect in this context.
Raw API responses
solver
{
"reasoning": "TIS11 (Tis11p) is a zinc finger RNA-binding protein that functions as an mRNA-binding translation repressor, homologous to the mammalian TTP (tristetraprolin) family. By binding to AU-rich elements (AREs) in target mRNAs and repressing their translation, TIS11 can dampen the expression of potentially harmful or pro-aging transcripts. Translation repression is a key mechanism for maintaining proteostasis by limiting the production of misfolded or aggregation-prone proteins. Additionally, global translational repression is a well-established pro-longevity mechanism in yeast and other organisms (e.g., via TOR pathway inhibition), and ARE-mediated mRNA regulation can suppress inflammatory or stress-response transcripts. The zinc ion binding activity is structural, supporting the CCCH-type zinc finger domains required for mRNA recognition. Overall, the translation repressor function aligns with pro-longevity roles seen for other translational regulators in yeast.",
"confidence": 0.55,
"key_pathways": [
"ARE-mediated mRNA translation repression",
"proteostasis via translational control",
"TOR-independent translational regulation"
],
"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 constructed a plausible-sounding but incorrect mechanistic argument, reasoning that translation repression generally promotes longevity. In reality, TIS11 in yeast is anti-longevity, meaning its deletion or loss extends lifespan. The model's reasoning about translational repression being pro-longevity is a general heuristic that doesn't apply here. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer. The mechanism proposed (proteostasis via translational control) is also incorrect in this context.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}