Hnrnpd
M. musculus
heterogeneous nuclear ribonucleoprotein D
What the model saw
Gene: Hnrnpd Organism: Mus musculus Known functions: heterogeneous nuclear ribonucleoprotein D. heterogeneous nuclear ribonucleoprotein D0. RNA binding. chromatin binding. histone deacetylase binding. mRNA 3'-UTR AU-rich region binding. mRNA binding. minor groove of adenine-thymine-rich DNA binding. nucleic acid binding. protein binding. telomeric repeat DNA binding.
View unredacted entry
heterogeneous nuclear ribonucleoprotein D. heterogeneous nuclear ribonucleoprotein D0. RNA binding. chromatin binding. histone deacetylase binding. mRNA 3'-UTR AU-rich region binding. mRNA binding. minor groove of adenine-thymine-rich DNA binding. nucleic acid binding. protein binding. telomeric repeat DNA binding.
Solver output
Hnrnpd (AUF1/hnRNP D0) binds telomeric repeat DNA, which is critical for telomere maintenance and protection against erosion — a hallmark of aging. Loss of AUF1/Hnrnpd in mice leads to premature aging phenotypes including telomere shortening, supporting a pro-longevity role for its normal function. Additionally, its binding to AU-rich elements (AREs) in mRNA 3'-UTRs regulates the stability of pro-inflammatory transcripts (e.g., TNF-α, IL-6), and AUF1 deficiency results in elevated inflammatory cytokine expression, linking it also to chronic inflammation. Its interaction with histone deacetylases further suggests roles in epigenetic regulation of gene expression relevant to aging. The convergence of telomere protection and suppression of inflammatory mRNA stability places its primary aging-relevant function at telomere maintenance.
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 pro_longevity for Hnrnpd/AUF1. The mechanistic reasoning is excellent and well-grounded: it correctly identifies AUF1's role in telomere maintenance (telomeric repeat DNA binding), its regulation of AU-rich element-containing inflammatory mRNAs (TNF-α, IL-6), and its interaction with histone deacetylases. The model accurately notes that AUF1 knockout mice show premature aging phenotypes including telomere shortening, which directly supports the pro-longevity classification. The confidence of 0.62 is reasonable given the complexity of the gene's functions. All key pathways cited are relevant and accurate.
Raw API responses
solver
{
"reasoning": "Hnrnpd (AUF1/hnRNP D0) binds telomeric repeat DNA, which is critical for telomere maintenance and protection against erosion — a hallmark of aging. Loss of AUF1/Hnrnpd in mice leads to premature aging phenotypes including telomere shortening, supporting a pro-longevity role for its normal function. Additionally, its binding to AU-rich elements (AREs) in mRNA 3'-UTRs regulates the stability of pro-inflammatory transcripts (e.g., TNF-α, IL-6), and AUF1 deficiency results in elevated inflammatory cytokine expression, linking it also to chronic inflammation. Its interaction with histone deacetylases further suggests roles in epigenetic regulation of gene expression relevant to aging. The convergence of telomere protection and suppression of inflammatory mRNA stability places its primary aging-relevant function at telomere maintenance.",
"confidence": 0.62,
"key_pathways": [
"Telomere maintenance and protection",
"AU-rich element-mediated mRNA decay (inflammatory cytokine suppression)",
"Epigenetic regulation via histone deacetylase interaction"
],
"mechanism_class": "telomere_attrition",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Hnrnpd/AUF1. The mechanistic reasoning is excellent and well-grounded: it correctly identifies AUF1's role in telomere maintenance (telomeric repeat DNA binding), its regulation of AU-rich element-containing inflammatory mRNAs (TNF-α, IL-6), and its interaction with histone deacetylases. The model accurately notes that AUF1 knockout mice show premature aging phenotypes including telomere shortening, which directly supports the pro-longevity classification. The confidence of 0.62 is reasonable given the complexity of the gene's functions. All key pathways cited are relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}