Peer Review #1 of "Deep conservation of prion-like composition in the eukaryotic prion-former Pub1/Tia1 family and its relatives (v0.1)"
Bibliographic record
Abstract
Pub1 protein is an important RNA-binding protein functional in stress granule assembly in budding yeast S. cerevisiae and, as its co-ortholog Tia1, in humans.It is unique among proteins in evidencing prion-like aggregation in both its yeast and human forms.Previously, we noted that Pub1/Tia1 was the only protein linked to human disease that has prion-like character and and has demonstrated such aggregation in both species.Thus, we were motivated to probe further into the evolution of the Pub1/Tia1 family (and its close relative Nam8 and its orthologs) to gain a picture of how such a protein has evolved over deep evolutionary time since the last common ancestor of eukaryotes.Here, we discover that the prion-like composition of this protein family is deeply conserved across eukaryotes, as is the prion-like composition of its close relative Nam8/Ngr1.A sizeable minority of protein orthologs have multiple prion-like domains within their sequences (6-20% depending on criteria).The number of RNA-binding RRM domains is conserved at three copies over >86% of the Pub1 family (>71% of the Nam8 family), but proteins with just one or two RRM domains occur frequently in some clades, indicating that these are not due to annotation errors.Overall, our results indicate that a basic scaffold comprising three RNA-binding domains and at least one prion-like region has been largely conserved since the last common ancestor of eukaryotes, providing further evidence that prion-like aggregation may be a very ancient and conserved phenomenon for certain specific proteins.
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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 | 0.011 | 0.100 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.005 | 0.002 |
| Science and technology studies | 0.005 | 0.002 |
| Scholarly communication | 0.008 | 0.004 |
| Open science | 0.003 | 0.004 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.296 | 0.242 |
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".