PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates
Bibliographic record
Abstract
ABSTRACT We have uncovered a novel role for the promyelocytic leukemia ( PML ) gene and novel PML-like DEDDh exonucleases in the maintenance of genome stability through the restriction of LINE-1 (L1) retrotransposition in jawed vertebrates. Although the PML tumour suppressor protein in mammals is SUMOylated and forms nuclear bodies, we found that the spotted gar PML ortholog and related proteins in fish are not SUMOylated and function as cytoplasmic DEDDh exonucleases. In contrast, more closely related avian and turtle PML proteins are predicted to be SUMOylated and localized both to the cytoplasm and to nuclear bodies. We also identified PML-like exon 9 ( Plex9 ) genes in teleost fishes that encode exonucleases sharing homology to gar PML. In an example of convergent evolution and akin to TREX1, gar PML and zebrafish Plex9 proteins suppressed L1 retrotransposition and could complement TREX1 knockout in mammalian cells. We also characterized the first non-mammalian TREX1 homologs in axolotl. Following export to the cytoplasm, the human PML-I isoform also restricted L1 through its conserved C-terminus and suppressed CGAS activation. Thus, PML first emerged as a cytoplasmic suppressor of retroelements, and this function is retained in amniotes despite its role in the assembly of nuclear bodies and the acquisition of SUMO-modification.
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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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".