rack-1
C. elegans
Small ribosomal subunit protein RACK1
What the model saw
Gene: rack-1 Organism: Caenorhabditis elegans Known functions: Small ribosomal subunit protein RACK1. protein binding. protein kinase C binding. ribosome binding. translation regulator activity.
View unredacted entry
Small ribosomal subunit protein RACK1. protein binding. protein kinase C binding. ribosome binding. translation regulator activity.
Solver output
RACK1 (Receptor for Activated C Kinase 1) is a scaffold protein embedded in the 40S ribosomal subunit that acts as a translation regulator and binds protein kinase C (PKC). In C. elegans, rack-1 promotes global mRNA translation by facilitating ribosome function and recruiting activated PKC to the ribosome, thereby stimulating cap-dependent translation. Enhanced translational activity is a hallmark of pro-growth, pro-aging signaling — analogous to elevated TOR/S6K activity — which accelerates proteostatic burden and shortens lifespan. Loss-of-function of ribosomal/translation components (e.g., rpl and rps subunits, rsks-1/S6K) consistently extends lifespan in C. elegans by reducing global protein synthesis rates. RACK1's role as a positive translation regulator and PKC effector at the ribosome places it in the nutrient-sensing/TOR axis that opposes longevity when active. Its PKC-binding function further links it to pro-growth signaling cascades that antagonize stress-resistance pathways such as DAF-16/FOXO.
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 anti_longevity for rack-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: RACK1 as a scaffold protein in the 40S ribosomal subunit that promotes translation, analogous to TOR/S6K activity, and the well-established finding that reducing translation extends lifespan in C. elegans. The PKC-binding connection to pro-growth signaling is also reasonable. The mechanism class "deregulated_nutrient_sensing" is a reasonable approximation, though "translation regulation" might be more precise. The reasoning draws appropriate parallels to known ribosomal/translation longevity regulators. Confidence of 0.72 is appropriate given the indirect reasoning. Overall a strong, well-reasoned prediction.
Raw API responses
solver
{
"reasoning": "RACK1 (Receptor for Activated C Kinase 1) is a scaffold protein embedded in the 40S ribosomal subunit that acts as a translation regulator and binds protein kinase C (PKC). In C. elegans, rack-1 promotes global mRNA translation by facilitating ribosome function and recruiting activated PKC to the ribosome, thereby stimulating cap-dependent translation. Enhanced translational activity is a hallmark of pro-growth, pro-aging signaling — analogous to elevated TOR/S6K activity — which accelerates proteostatic burden and shortens lifespan. Loss-of-function of ribosomal/translation components (e.g., rpl and rps subunits, rsks-1/S6K) consistently extends lifespan in C. elegans by reducing global protein synthesis rates. RACK1's role as a positive translation regulator and PKC effector at the ribosome places it in the nutrient-sensing/TOR axis that opposes longevity when active. Its PKC-binding function further links it to pro-growth signaling cascades that antagonize stress-resistance pathways such as DAF-16/FOXO.",
"confidence": 0.72,
"key_pathways": [
"mTOR/translation regulation via 40S ribosome",
"Protein kinase C (PKC) signaling",
"Cap-dependent mRNA translation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for rack-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: RACK1 as a scaffold protein in the 40S ribosomal subunit that promotes translation, analogous to TOR/S6K activity, and the well-established finding that reducing translation extends lifespan in C. elegans. The PKC-binding connection to pro-growth signaling is also reasonable. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable approximation, though \"translation regulation\" might be more precise. The reasoning draws appropriate parallels to known ribosomal/translation longevity regulators. Confidence of 0.72 is appropriate given the indirect reasoning. Overall a strong, well-reasoned prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}