UAF30
S. cerevisiae
Uaf30p
What the model saw
Gene: UAF30 Organism: Saccharomyces cerevisiae Known functions: Uaf30p. RNA polymerase I cis-regulatory region sequence-specific DNA binding. RNA polymerase I general transcription initiation factor activity.
View unredacted entry
Uaf30p. RNA polymerase I cis-regulatory region sequence-specific DNA binding. RNA polymerase I general transcription initiation factor activity.
Solver output
UAF30 encodes a subunit of the Upstream Activation Factor (UAF) complex in S. cerevisiae, which binds cis-regulatory elements in rDNA promoters and acts as a general transcription initiation factor for RNA Polymerase I. Elevated rDNA transcription by Pol I drives ribosome biogenesis, a major anabolic output that is tightly coupled to TOR signaling and nutrient sensing. Increased ribosomal RNA production and ribosome biogenesis are well-established pro-aging factors in yeast; conversely, reduced Pol I activity or rDNA silencing extends lifespan. Furthermore, the rDNA locus is a hotspot for epigenetic instability and extrachromosomal rDNA circle (ERC) formation, a key driver of replicative aging in yeast. By promoting Pol I transcription initiation at rDNA, UAF30 likely accelerates aging through increased ribosome biogenesis and potential destabilization of rDNA chromatin structure.
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 UAF30. The mechanistic reasoning is sound and well-articulated: UAF30 as a UAF complex subunit promotes Pol I transcription at rDNA, which drives ribosome biogenesis (a pro-aging factor in yeast), and may also destabilize rDNA chromatin contributing to ERC formation. The classification as "epigenetic_alterations" is somewhat debatable since the primary mechanism is transcriptional activation of rDNA rather than epigenetic modification per se, but the connection to rDNA chromatin stability and ERC formation makes this partially justified. The reasoning correctly identifies the key pathways linking Pol I activity to aging in yeast. Confidence of 0.62 is appropriately calibrated for a less well-known gene.
Raw API responses
solver
{
"reasoning": "UAF30 encodes a subunit of the Upstream Activation Factor (UAF) complex in S. cerevisiae, which binds cis-regulatory elements in rDNA promoters and acts as a general transcription initiation factor for RNA Polymerase I. Elevated rDNA transcription by Pol I drives ribosome biogenesis, a major anabolic output that is tightly coupled to TOR signaling and nutrient sensing. Increased ribosomal RNA production and ribosome biogenesis are well-established pro-aging factors in yeast; conversely, reduced Pol I activity or rDNA silencing extends lifespan. Furthermore, the rDNA locus is a hotspot for epigenetic instability and extrachromosomal rDNA circle (ERC) formation, a key driver of replicative aging in yeast. By promoting Pol I transcription initiation at rDNA, UAF30 likely accelerates aging through increased ribosome biogenesis and potential destabilization of rDNA chromatin structure.",
"confidence": 0.62,
"key_pathways": [
"RNA Polymerase I transcription / rDNA promoter activation",
"Ribosome biogenesis (TOR-coupled anabolic signaling)",
"rDNA chromatin stability and ERC formation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for UAF30. The mechanistic reasoning is sound and well-articulated: UAF30 as a UAF complex subunit promotes Pol I transcription at rDNA, which drives ribosome biogenesis (a pro-aging factor in yeast), and may also destabilize rDNA chromatin contributing to ERC formation. The classification as \"epigenetic_alterations\" is somewhat debatable since the primary mechanism is transcriptional activation of rDNA rather than epigenetic modification per se, but the connection to rDNA chromatin stability and ERC formation makes this partially justified. The reasoning correctly identifies the key pathways linking Pol I activity to aging in yeast. Confidence of 0.62 is appropriately calibrated for a less well-known gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}