MétaCan
Menu
Back to cohort
Record W4404459069 · doi:10.1016/j.jbc.2024.108000

Proteomic study identifies Aurora-A–mediated regulation of alternative splicing through multiple splicing factors

2024· article· en· W4404459069 on OpenAlexaff
Arun Prasath Damodaran, Olivia Gavard, Jean‐Philippe Gagné, Malgorzata Ewa Rogalska, Amit K. Behera, Estefanía Mancini, Giulia Bertolin, Thibault Courthéoux, Bandana Kumari, Justine Cailloce, Agnès Méreau, Guy G. Poirier, Juan Valcárcel, Thomas Gonatopoulos-Pournatzis, Erwan Watrin, Claude Prigent

Bibliographic record

VenueJournal of Biological Chemistry · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsHôtel-Dieu de QuébecCentre hospitalier universitaire de Québec
FundersMinisterio de Ciencia e InnovaciónNational Cancer InstituteNational Institutes of HealthGeneralitat de CatalunyaCentres de Recerca de CatalunyaAgencia Estatal de InvestigaciónUniversité de Rennes 1Ministerio de Ciencia, Innovación y UniversidadesLigue Contre le CancerCentre National de la Recherche ScientifiqueEuropean Molecular Biology Laboratory
KeywordsAlternative splicingRNA splicingComputational biologySplicing factorBiologyGeneticsCell biologyBioinformaticsGeneExonRNA

Abstract

fetched live from OpenAlex

The cell cycle regulator Aurora-A kinase presents an attractive target for cancer therapies, though its inhibition is also associated with toxic side effects. To gain a more nuanced understanding of Aurora-A function, we applied shotgun proteomics to identify 407 specific protein partners, including several splicing factors. Supporting a role in alternative splicing, we found that Aurora-A localizes to nuclear speckles, the storehouse of splicing proteins. Aurora-A interacts with and phosphorylates splicing factors both in vitro and in vivo, suggesting that it regulates alternative splicing by modulating the activity of these splicing factors. Consistently, Aurora-A inhibition significantly impacts the alternative splicing of 505 genes, with RNA motif analysis revealing an enrichment for Aurora-A interacting splicing factors. Additionally, we observed a significant positive correlation between the splicing events regulated by Aurora-A and those modulated by its interacting splicing factors. An interesting example is represented by CLK1 exon 4, which appears to be regulated by Aurora-A through SRSF3. Collectively, our findings highlight a broad role of Aurora-A in the regulation of alternative splicing.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.038
GPT teacher head0.317
Teacher spread0.279 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations13
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Biological ChemistrySame topicRNA Research and SplicingFrench-language works237,207