SPT4

S. cerevisiae

transcription elongation factor SPT4

What the model saw

Gene: SPT4
Organism: Saccharomyces cerevisiae
Known functions: transcription elongation factor SPT4. RNA polymerase II complex binding. protein binding. protein-containing complex binding. rDNA binding. single-stranded RNA binding. zinc ion binding.

View unredacted entry

transcription elongation factor SPT4. RNA polymerase II complex binding. protein binding. protein-containing complex binding. rDNA binding. single-stranded RNA binding. zinc ion binding.

Solver output

Predicted influence

Pro-longevity

Confidence

62%

Mechanism

Epigenetic alterations

Reasoning

SPT4 is a transcription elongation factor that forms the DSIF complex with SPT5, directly binding RNA Pol II to regulate transcriptional elongation and pausing. Its rDNA binding activity is particularly relevant to yeast aging: proper transcriptional regulation at the rDNA locus is critical for maintaining rDNA stability and suppressing the formation of extrachromosomal rDNA circles (ERCs), a key driver of replicative aging in S. cerevisiae. SPT4-mediated elongation fidelity also supports proteostasis by ensuring accurate mRNA production. Loss of SPT4 function has been associated with transcriptional stress and dysregulation at repetitive loci, which would accelerate aging phenotypes. Its zinc ion binding is consistent with a structural role in the DSIF complex necessary for proper chromatin-associated transcription regulation.

Key pathways

rDNA transcription regulation / ERC suppressionRNA Pol II transcription elongation (DSIF complex)chromatin-associated transcriptional fidelity

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted SPT4 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning assumed that SPT4 loss would accelerate aging (making it pro_longevity when present), but in reality SPT4 is anti_longevity, meaning its presence shortens lifespan or its deletion extends lifespan. The model's mechanistic reasoning about rDNA stability and ERC suppression was speculative and ultimately pointed in the wrong direction. The model was moderately confident (0.62) in an incorrect answer. The reasoning about DSIF complex and rDNA binding is plausible-sounding but led to the wrong conclusion about the direction of effect on longevity.

Raw API responses

solver

{
  "reasoning": "SPT4 is a transcription elongation factor that forms the DSIF complex with SPT5, directly binding RNA Pol II to regulate transcriptional elongation and pausing. Its rDNA binding activity is particularly relevant to yeast aging: proper transcriptional regulation at the rDNA locus is critical for maintaining rDNA stability and suppressing the formation of extrachromosomal rDNA circles (ERCs), a key driver of replicative aging in S. cerevisiae. SPT4-mediated elongation fidelity also supports proteostasis by ensuring accurate mRNA production. Loss of SPT4 function has been associated with transcriptional stress and dysregulation at repetitive loci, which would accelerate aging phenotypes. Its zinc ion binding is consistent with a structural role in the DSIF complex necessary for proper chromatin-associated transcription regulation.",
  "confidence": 0.62,
  "key_pathways": [
    "rDNA transcription regulation / ERC suppression",
    "RNA Pol II transcription elongation (DSIF complex)",
    "chromatin-associated transcriptional fidelity"
  ],
  "mechanism_class": "epigenetic_alterations",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted SPT4 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning assumed that SPT4 loss would accelerate aging (making it pro_longevity when present), but in reality SPT4 is anti_longevity, meaning its presence shortens lifespan or its deletion extends lifespan. The model's mechanistic reasoning about rDNA stability and ERC suppression was speculative and ultimately pointed in the wrong direction. The model was moderately confident (0.62) in an incorrect answer. The reasoning about DSIF complex and rDNA binding is plausible-sounding but led to the wrong conclusion about the direction of effect on longevity.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}