Structural insights into a regulatory mechanism of FIR RRM1–FUSE interaction
Bibliographic record
Abstract
FUBP-interacting repressor (FIR) is a suppressor of transcription of the proto-oncogene MYC. FIR binds to the far upstream element (FUSE) of the MYC promoter. Competition of FIR with FUSE-binding protein 1 (FUBP1) is a key mechanism of MYC transcriptional regulation. To gain insights into the structural mechanisms regulating FIR DNA interaction, we determined the crystal structure of two FIR RRM domains (RRM1-2) with single-stranded FUSE DNA sequences. These structures revealed an ability of the RRM domain to recognize diverse FUSE regions through distinct intermolecular interactions and binding modes. Comparative structural analyses against available RRM-ssDNA/RNA complexes showed that the nucleotide configurations in FIR were similar to those in other RRMs that harbour a tyrosine at the conserved aromatic position in the RNP2 motif (Y-type RRM), but not those with a phenylalanine (F-type RRM). Site-directed mutagenesis experiments demonstrated that a single substitution, Y115F, altered the binding affinities of oligonucleotides to FIR RRM, suggesting an important role of this conserved aromatic residue in ssDNA/RNA interactions. Our study provides the structural basis for further mechanistic studies on this important protein-DNA interaction.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".