Sticky DNA, a Self-associated Complex Formed at Long GAA·TTC Repeats in Intron 1 of the Frataxin Gene, Inhibits Transcription
Bibliographic record
Abstract
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by the expansion of GAA.TTC repeats in the first intron of the frataxin (X25) gene. FRDA patients carrying two expanded GAA.TTC repeats show very low levels of mature frataxin mRNA and protein. A novel type of unusual DNA structure, sticky DNA, was previously found in the expanded GAA.TTC repeats from FRDA patients. To evaluate the effect of sticky DNA on transcription, in vitro transcription studies of (GAA.TTC)(n) repeats (where n = 9-150) were carried out using T7 or SP6 RNA polymerase. When a gel-isolated sticky DNA template was transcribed, the amount of full-length RNA synthesized was significantly reduced compared with the transcription of the linear template. Surprisingly, transcriptional inhibition was observed not only for the sticky DNA template but also another DNA molecule used as an internal control in an orientation-independent manner. The molecular mechanism of transcriptional inhibition by sticky DNA was a sequestration of the RNA polymerases by direct binding to the complex DNA structure. Moreover, plasmids containing the (GAAGGA.TCCTTC)(65) repeat, which does not form sticky DNA, did not inhibit in vitro transcription, as expected. These results suggest that the role of sticky DNA in FRDA may be the sequestration of transcription factors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".