hel-1
C. elegans
Spliceosome RNA helicase DDX39B homolog
What the model saw
Gene: hel-1 Organism: Caenorhabditis elegans Known functions: Spliceosome RNA helicase DDX39B homolog. ATP binding. ATP hydrolysis activity. RNA helicase activity. RNA polymerase II-specific DNA-binding transcription factor binding. mRNA binding. nucleic acid binding.
View unredacted entry
Spliceosome RNA helicase DDX39B homolog. ATP binding. ATP hydrolysis activity. RNA helicase activity. RNA polymerase II-specific DNA-binding transcription factor binding. mRNA binding. nucleic acid binding.
Solver output
hel-1 encodes a DDX39B homolog, an ATP-dependent RNA helicase essential for pre-mRNA splicing (spliceosome function) and mRNA export. Accurate pre-mRNA splicing is critical for maintaining the transcriptome integrity and proteostasis; defects in splicing fidelity are associated with aging and age-related decline in C. elegans. The interaction with RNA Pol II-specific transcription factors suggests hel-1 also participates in transcription-coupled RNA processing, linking it to proper gene expression regulation. Loss of spliceosome helicase activity leads to aberrant splicing, accumulation of mis-spliced transcripts, and downstream proteotoxic stress — hallmarks of cellular aging. DDX39B orthologs also facilitate nuclear mRNA export, and impaired mRNA export disrupts stress-response pathways (e.g., HSF-1, DAF-16) that are central to longevity in C. elegans. Therefore, normal hel-1 function supports transcriptome fidelity and stress-response gene expression, promoting 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 predicted pro_longevity for hel-1. The mechanistic reasoning is plausible and well-grounded: hel-1 as a DDX39B homolog involved in spliceosome function, mRNA export, and transcriptome fidelity, with connections to proteostasis and stress-response pathways (HSF-1, DAF-16) relevant to C. elegans longevity. The mechanism class of "epigenetic_alterations" is a slight mismatch — splicing/RNA processing is more accurately classified as post-transcriptional regulation rather than epigenetic alterations — but the narrative reasoning itself is sound. Confidence of 0.62 is appropriately moderate given the limited direct evidence in the entry.
Raw API responses
solver
{
"reasoning": "hel-1 encodes a DDX39B homolog, an ATP-dependent RNA helicase essential for pre-mRNA splicing (spliceosome function) and mRNA export. Accurate pre-mRNA splicing is critical for maintaining the transcriptome integrity and proteostasis; defects in splicing fidelity are associated with aging and age-related decline in C. elegans. The interaction with RNA Pol II-specific transcription factors suggests hel-1 also participates in transcription-coupled RNA processing, linking it to proper gene expression regulation. Loss of spliceosome helicase activity leads to aberrant splicing, accumulation of mis-spliced transcripts, and downstream proteotoxic stress — hallmarks of cellular aging. DDX39B orthologs also facilitate nuclear mRNA export, and impaired mRNA export disrupts stress-response pathways (e.g., HSF-1, DAF-16) that are central to longevity in C. elegans. Therefore, normal hel-1 function supports transcriptome fidelity and stress-response gene expression, promoting longevity.",
"confidence": 0.62,
"key_pathways": [
"pre-mRNA splicing / spliceosome integrity",
"mRNA export and transcriptome fidelity",
"RNA Pol II transcription-coupled RNA processing"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for hel-1. The mechanistic reasoning is plausible and well-grounded: hel-1 as a DDX39B homolog involved in spliceosome function, mRNA export, and transcriptome fidelity, with connections to proteostasis and stress-response pathways (HSF-1, DAF-16) relevant to C. elegans longevity. The mechanism class of \"epigenetic_alterations\" is a slight mismatch — splicing/RNA processing is more accurately classified as post-transcriptional regulation rather than epigenetic alterations — but the narrative reasoning itself is sound. Confidence of 0.62 is appropriately moderate given the limited direct evidence in the entry.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}