crn-5
C. elegans
Exosome complex component RRP46 homolog
What the model saw
Gene: crn-5 Organism: Caenorhabditis elegans Known functions: Exosome complex component RRP46 homolog. 3'-5' exonuclease activity. RNA binding. double-stranded DNA binding. enzyme binding.
View unredacted entry
Exosome complex component RRP46 homolog. 3'-5' exonuclease activity. RNA binding. double-stranded DNA binding. enzyme binding.
Solver output
crn-5 encodes the C. elegans homolog of RRP46, a structural and catalytic component of the RNA exosome complex that harbors 3'-5' exonuclease activity. The RNA exosome is essential for RNA surveillance, degrading aberrant, misprocessed, or excess RNA species including rRNA, mRNA, and non-coding RNAs. Proper RNA quality control prevents the accumulation of defective transcripts that could be translated into aberrant proteins, thereby supporting proteostasis and reducing cellular stress. Additionally, the exosome participates in DNA damage response pathways (consistent with the double-stranded DNA binding annotation), helping to resolve R-loops and transcription-replication conflicts that contribute to genomic instability. Loss of exosome function in model organisms is associated with accelerated aging phenotypes, suggesting that crn-5/RRP46 normally acts to maintain RNA and genome integrity, 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that loss of exosome function leads to accelerated aging, implying crn-5 is pro-longevity. However, the actual GenAge classification is anti_longevity, meaning crn-5 normally limits lifespan (i.e., its loss or reduction extends lifespan). The model's mechanistic reasoning about RNA surveillance and proteostasis is plausible in general but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still clearly wrong on the direction of effect. The reasoning quality is low because it failed to consider that RNA exosome components can also suppress longevity pathways or that RNAi knockdown of crn-5 might extend lifespan in C. elegans.
Raw API responses
solver
{
"reasoning": "crn-5 encodes the C. elegans homolog of RRP46, a structural and catalytic component of the RNA exosome complex that harbors 3'-5' exonuclease activity. The RNA exosome is essential for RNA surveillance, degrading aberrant, misprocessed, or excess RNA species including rRNA, mRNA, and non-coding RNAs. Proper RNA quality control prevents the accumulation of defective transcripts that could be translated into aberrant proteins, thereby supporting proteostasis and reducing cellular stress. Additionally, the exosome participates in DNA damage response pathways (consistent with the double-stranded DNA binding annotation), helping to resolve R-loops and transcription-replication conflicts that contribute to genomic instability. Loss of exosome function in model organisms is associated with accelerated aging phenotypes, suggesting that crn-5/RRP46 normally acts to maintain RNA and genome integrity, promoting longevity.",
"confidence": 0.62,
"key_pathways": [
"RNA exosome-mediated RNA surveillance",
"RNA quality control and proteostasis",
"R-loop resolution and genomic stability"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that loss of exosome function leads to accelerated aging, implying crn-5 is pro-longevity. However, the actual GenAge classification is anti_longevity, meaning crn-5 normally limits lifespan (i.e., its loss or reduction extends lifespan). The model's mechanistic reasoning about RNA surveillance and proteostasis is plausible in general but leads to the wrong conclusion for this specific gene. The model had moderate confidence (0.62) but was still clearly wrong on the direction of effect. The reasoning quality is low because it failed to consider that RNA exosome components can also suppress longevity pathways or that RNAi knockdown of crn-5 might extend lifespan in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}