pash-1
C. elegans
DRBM domain-containing protein
What the model saw
Gene: pash-1 Organism: Caenorhabditis elegans Known functions: DRBM domain-containing protein. RNA binding. double-stranded RNA binding. heme binding. identical protein binding. primary miRNA binding.
View unredacted entry
DRBM domain-containing protein. RNA binding. double-stranded RNA binding. heme binding. identical protein binding. primary miRNA binding.
Solver output
pash-1 is the C. elegans ortholog of DGCR8/Pasha, the dsRNA-binding partner of Drosha in the Microprocessor complex responsible for processing primary miRNAs (pri-miRNAs) into precursor miRNAs (pre-miRNAs). Its annotated functions — primary miRNA binding, double-stranded RNA binding, and DRBM domain — are hallmarks of this role. Proper miRNA biogenesis via the Microprocessor complex is essential for the production of key longevity-promoting miRNAs in C. elegans, including lin-4 and miR-71, which suppress pro-aging targets such as lin-14 and components of the insulin/IGF-1 signaling pathway. Loss of pash-1 function disrupts global miRNA maturation, leading to derepression of aging-promoting transcripts and shortened lifespan, as demonstrated in studies where pash-1 hypomorphic mutants are short-lived. Thus, the normal function of pash-1 supports longevity by enabling the miRNA-mediated post-transcriptional silencing of pro-aging gene networks.
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 pash-1 as pro_longevity. The mechanistic reasoning is detailed and accurate: pash-1 is indeed the C. elegans ortholog of DGCR8/Pasha, functioning as part of the Microprocessor complex for pri-miRNA processing. The model correctly identifies that loss of pash-1 disrupts miRNA biogenesis, leading to derepression of pro-aging targets and shortened lifespan. The specific examples of longevity-promoting miRNAs (lin-4, miR-71) and their targets are accurate. The classification as "epigenetic_alterations" is a reasonable categorization for miRNA-mediated gene regulation, though "post-transcriptional regulation" might be more precise. Overall, this is a high-quality, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "pash-1 is the C. elegans ortholog of DGCR8/Pasha, the dsRNA-binding partner of Drosha in the Microprocessor complex responsible for processing primary miRNAs (pri-miRNAs) into precursor miRNAs (pre-miRNAs). Its annotated functions — primary miRNA binding, double-stranded RNA binding, and DRBM domain — are hallmarks of this role. Proper miRNA biogenesis via the Microprocessor complex is essential for the production of key longevity-promoting miRNAs in C. elegans, including lin-4 and miR-71, which suppress pro-aging targets such as lin-14 and components of the insulin/IGF-1 signaling pathway. Loss of pash-1 function disrupts global miRNA maturation, leading to derepression of aging-promoting transcripts and shortened lifespan, as demonstrated in studies where pash-1 hypomorphic mutants are short-lived. Thus, the normal function of pash-1 supports longevity by enabling the miRNA-mediated post-transcriptional silencing of pro-aging gene networks.",
"confidence": 0.72,
"key_pathways": [
"pri-miRNA processing / Microprocessor complex",
"insulin/IGF-1 signaling pathway (miRNA-mediated regulation)",
"miRNA biogenesis (lin-4, miR-71 maturation)"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pash-1 as pro_longevity. The mechanistic reasoning is detailed and accurate: pash-1 is indeed the C. elegans ortholog of DGCR8/Pasha, functioning as part of the Microprocessor complex for pri-miRNA processing. The model correctly identifies that loss of pash-1 disrupts miRNA biogenesis, leading to derepression of pro-aging targets and shortened lifespan. The specific examples of longevity-promoting miRNAs (lin-4, miR-71) and their targets are accurate. The classification as \"epigenetic_alterations\" is a reasonable categorization for miRNA-mediated gene regulation, though \"post-transcriptional regulation\" might be more precise. Overall, this is a high-quality, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}