The discovery and characterization of two novel structural motifs on the carboxy-terminal domain of kinetoplastid RNA editing ligases
Bibliographic record
Abstract
species have a uniquely organized mitochondrial genome, the kinetoplast. Most kinetoplast-transcribed mRNAs are cryptic and encode multiple subunits for the electron transport chain following maturation through a uridine insertion/deletion process called RNA editing. This process is achieved through an enzyme cascade by an RNA editing catalytic complex (RECC), where the final ligation step is catalyzed by the kinetoplastid RNA editing ligases, KREL1 and KREL2. While the amino-terminal domain (NTD) of these proteins is highly conserved with other DNA ligases and mRNA capping enzymes, with five recognizable motifs, the functional role of their diverged carboxy-terminal domain (CTD) has remained elusive. In this manuscript, we assayed recombinant KREL1 in vitro to unveil critical residues from its CTD to be involved in protein-protein interaction and dsRNA ligation activity. Our data show that the α-helix (H)3 of KREL1 CTD interacts with the αH1 of its editosome protein partner KREPA2. Intriguingly, the OB-fold domain and the zinc fingers on KREPA2 do not appear to influence the RNA ligation activity of KREL1. Moreover, a specific KWKE motif on the αH4 of KREL1 CTD is found to be implicated in ligase auto-adenylylation analogous to motif VI in DNA ligases. In summary, we present in the KREL1 CTD a motif VI for auto-adenylylation and a KREPA2 binding motif for RECC integration.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".