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Record W4412707885 · doi:10.1038/s41587-025-02733-6

A resource of RNA-binding protein motifs across eukaryotes reveals evolutionary dynamics and gene-regulatory function

2025· article· en· W4412707885 on OpenAlexafffund
Alexander Sasse, Debashish Ray, Kaitlin U. Laverty, Cyrus L. Tam, Mihai Albu, Yevgen Levdansky, Olga Lyudovyk, Taykhoom Dalal, Kate Nie, Cedrik Magis, Cédric Notredame, Eugene Valkov, Matthew T. Weirauch, Timothy R. Hughes, Quaid Morris

Bibliographic record

VenueNature Biotechnology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA and protein synthesis mechanisms
Canadian institutionsVector InstituteOntario Institute for Cancer ResearchUniversity of Toronto
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Allergy and Infectious DiseasesNational Science FoundationCanadian Institutes of Health ResearchMitacsUniversity of TorontoNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human ServicesGovernment of CanadaCincinnati Children's Hospital Medical CenterNational Human Genome Research Institute
KeywordsFunction (biology)GeneBiologyComputational biologyRNADynamics (music)Regulation of gene expressionEvolutionary biologyRNA-binding proteinEvolutionary dynamicsGenetics

Abstract

fetched live from OpenAlex

RNA-binding proteins (RBPs) are key regulators of gene expression; however, their RNA-binding specificities, that is, motifs, have not been comprehensively determined. Here we introduce Eukaryotic Protein-RNA Interactions (EuPRI), a freely available resource of RNA motifs for 34,746 RBPs from 690 eukaryotes. EuPRI includes in vitro binding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of predicted motifs. We predict these motifs with an algorithm, Joint Protein-Ligand Embedding, which can detect distant homology relationships and map specificity-determining peptides. EuPRI quadruples the number of available RBP motifs, expanding the motif repertoire across all major eukaryotic clades and assigning motifs to the majority of human RBPs. We demonstrate the utility of EuPRI for inferring post-transcriptional function and evolutionary relationships by identifying rapid, recent evolution of post-transcriptional regulatory networks in worms and plants, in contrast to the vertebrate RNA motif set, which has remained relatively stable after a large expansion between the metazoan and vertebrate ancestors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesResearch integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.027
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0020.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.003
GPT teacher head0.227
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations12
Published2025
Admission routes2
Has abstractyes

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