alg-2
C. elegans
Protein argonaute-1
What the model saw
Gene: alg-2 Organism: Caenorhabditis elegans Known functions: Protein argonaute-1. RNA binding. RNA endonuclease activity. RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism. double-stranded RNA binding. endoribonuclease activity, cleaving siRNA-paired mRNA. miRNA binding. nucleic acid binding. single-stranded RNA binding.
View unredacted entry
Protein argonaute-1. RNA binding. RNA endonuclease activity. RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism. double-stranded RNA binding. endoribonuclease activity, cleaving siRNA-paired mRNA. miRNA binding. nucleic acid binding. single-stranded RNA binding.
Solver output
alg-2 encodes Argonaute-1 in C. elegans, a core component of the RNA-induced silencing complex (RISC) that mediates miRNA- and siRNA-directed post-transcriptional gene silencing. By binding miRNAs and cleaving complementary target mRNAs via its endonuclease (Slicer) activity, ALG-2 enforces precise gene expression programs that are critical for developmental timing and stress responses. In C. elegans, the miRNA pathway (including let-7 and its targets) is well-established as a regulator of lifespan and aging; loss of Argonaute function disrupts miRNA-mediated silencing of pro-aging targets such as components of the insulin/IGF-1 signaling pathway. Argonaute proteins also participate in small RNA-mediated epigenetic inheritance and transgenerational silencing, which contribute to genome integrity and proteostasis maintenance. The net effect of intact ALG-2/Argonaute-1 function is therefore to support the silencing of genes that would otherwise accelerate aging, placing it in a pro-longevity role.
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 alg-2 in C. elegans with reasonable confidence (0.72). The mechanistic reasoning is sound - alg-2 encodes Argonaute-1, a core RISC component involved in miRNA/siRNA-mediated gene silencing, and the model correctly connects this to lifespan regulation through silencing of pro-aging targets. The model also mentions epigenetic inheritance and transgenerational silencing, which is relevant. The mechanism_class of "epigenetic_alterations" is somewhat debatable (RNA silencing/post-transcriptional regulation might be more precise), but it's not entirely wrong given the epigenetic inheritance aspect mentioned. The reasoning about let-7 and insulin/IGF-1 pathway regulation is plausible and well-grounded in C. elegans biology. Overall a solid prediction with good reasoning.
Raw API responses
solver
{
"reasoning": "alg-2 encodes Argonaute-1 in C. elegans, a core component of the RNA-induced silencing complex (RISC) that mediates miRNA- and siRNA-directed post-transcriptional gene silencing. By binding miRNAs and cleaving complementary target mRNAs via its endonuclease (Slicer) activity, ALG-2 enforces precise gene expression programs that are critical for developmental timing and stress responses. In C. elegans, the miRNA pathway (including let-7 and its targets) is well-established as a regulator of lifespan and aging; loss of Argonaute function disrupts miRNA-mediated silencing of pro-aging targets such as components of the insulin/IGF-1 signaling pathway. Argonaute proteins also participate in small RNA-mediated epigenetic inheritance and transgenerational silencing, which contribute to genome integrity and proteostasis maintenance. The net effect of intact ALG-2/Argonaute-1 function is therefore to support the silencing of genes that would otherwise accelerate aging, placing it in a pro-longevity role.",
"confidence": 0.72,
"key_pathways": [
"miRNA-mediated post-transcriptional gene silencing (RISC)",
"siRNA pathway / RNA interference",
"insulin/IGF-1 signaling pathway regulation via miRNA targeting"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for alg-2 in C. elegans with reasonable confidence (0.72). The mechanistic reasoning is sound - alg-2 encodes Argonaute-1, a core RISC component involved in miRNA/siRNA-mediated gene silencing, and the model correctly connects this to lifespan regulation through silencing of pro-aging targets. The model also mentions epigenetic inheritance and transgenerational silencing, which is relevant. The mechanism_class of \"epigenetic_alterations\" is somewhat debatable (RNA silencing/post-transcriptional regulation might be more precise), but it's not entirely wrong given the epigenetic inheritance aspect mentioned. The reasoning about let-7 and insulin/IGF-1 pathway regulation is plausible and well-grounded in C. elegans biology. Overall a solid prediction with good reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}