RPD3
S. cerevisiae
histone deacetylase RPD3
What the model saw
Gene: RPD3 Organism: Saccharomyces cerevisiae Known functions: histone deacetylase RPD3. histone deacetylase activity. histone deacetylase activity, hydrolytic mechanism. protein binding. transcription coactivator activity. transcription corepressor activity. zinc ion binding.
View unredacted entry
histone deacetylase RPD3. histone deacetylase activity. histone deacetylase activity, hydrolytic mechanism. protein binding. transcription coactivator activity. transcription corepressor activity. zinc ion binding.
Solver output
RPD3 is the founding class I histone deacetylase (HDAC) in S. cerevisiae, catalyzing the removal of acetyl groups from histone H3 and H4 lysine residues via a zinc-dependent hydrolytic mechanism. Deacetylation by RPD3 represses transcription at target loci, including genes involved in stress response and nutrient sensing. Critically, deletion of RPD3 extends replicative lifespan in yeast, and this extension is epistatic with caloric restriction, placing RPD3 in the same pathway as nutrient-sensing longevity regulation. RPD3 activity suppresses the expression of genes that promote longevity (e.g., those involved in autophagy and stress resistance) and its repression of ribosomal protein genes under caloric restriction is a key mechanism linking nutrient sensing to lifespan. Thus, the normal function of RPD3 — chromatin compaction via histone deacetylation and transcriptional repression — opposes 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 correctly identifies RPD3 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: RPD3 is indeed a class I HDAC in yeast whose deletion extends replicative lifespan, and the model correctly places it in the caloric restriction/nutrient sensing pathway. The explanation of epistasis with caloric restriction, the role in repressing stress-response and autophagy genes, and the connection to ribosomal protein gene regulation are all well-established findings in the yeast aging literature. The mechanism class (epigenetic_alterations) is appropriate.
Raw API responses
solver
{
"reasoning": "RPD3 is the founding class I histone deacetylase (HDAC) in S. cerevisiae, catalyzing the removal of acetyl groups from histone H3 and H4 lysine residues via a zinc-dependent hydrolytic mechanism. Deacetylation by RPD3 represses transcription at target loci, including genes involved in stress response and nutrient sensing. Critically, deletion of RPD3 extends replicative lifespan in yeast, and this extension is epistatic with caloric restriction, placing RPD3 in the same pathway as nutrient-sensing longevity regulation. RPD3 activity suppresses the expression of genes that promote longevity (e.g., those involved in autophagy and stress resistance) and its repression of ribosomal protein genes under caloric restriction is a key mechanism linking nutrient sensing to lifespan. Thus, the normal function of RPD3 — chromatin compaction via histone deacetylation and transcriptional repression — opposes longevity.",
"confidence": 0.92,
"key_pathways": [
"histone deacetylation / chromatin remodeling",
"caloric restriction / nutrient sensing (TOR pathway)",
"transcriptional repression of stress-response genes"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies RPD3 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: RPD3 is indeed a class I HDAC in yeast whose deletion extends replicative lifespan, and the model correctly places it in the caloric restriction/nutrient sensing pathway. The explanation of epistasis with caloric restriction, the role in repressing stress-response and autophagy genes, and the connection to ribosomal protein gene regulation are all well-established findings in the yeast aging literature. The mechanism class (epigenetic_alterations) is appropriate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}