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Record W3183452172 · doi:10.1021/jacs.1c04194

<i>O</i>-Linked-<i>N</i>-Acetylglucosaminylation of the RNA-Binding Protein EWS N-Terminal Low Complexity Region Reduces Phase Separation and Enhances Condensate Dynamics

2021· article· en· W3183452172 on OpenAlexafffund
Michael L. Nosella, Maria Tereshchenko, Iva Pritišanac, P. Andrew Chong, Jeffrey A. Toretsky, Hyun O. Lee, Julie D. Forman‐Kay

Bibliographic record

VenueJournal of the American Chemical Society · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsHospital for Sick ChildrenUniversity of Toronto
FundersNational Cancer InstituteNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchUniversity of TorontoCanadian Cancer SocietyCanada Research ChairsChildren's Cancer Foundation
KeywordsChemistryBiophysicsFluorescence recovery after photobleachingRNAIntrinsically disordered proteinsStress granuleOrganelleBiochemistryTranslation (biology)Messenger RNA

Abstract

fetched live from OpenAlex

Many membraneless organelles are thought to be biomolecular condensates formed by phase separation of proteins and other biopolymers. Post-translational modifications (PTMs) can impact protein phase separation behavior, although for many PTMs this aspect of their function is unknown. O -linked β-D- N -acetylglucosaminylation ( O -GlcNAcylation) is an abundant form of intracellular glycosylation whose roles in regulating biomolecular condensate assembly and dynamics have not been delineated. Using an in vitro approach, we found that O -GlcNAcylation reduces the phase separation propensity of the EWS N -terminal low complexity region (LCR N ) under different conditions, including in the presence of the arginine- and glycine-rich RNA-binding domains (RBD). O -GlcNAcylation enhances fluorescence recovery after photobleaching (FRAP) within EWS LCR N condensates and causes the droplets to exhibit more liquid-like relaxation following fusion. Following extended incubation times, EWS LCR N +RBD condensates exhibit diminished FRAP, indicating a loss of fluidity, while condensates containing the O -GlcNAcylated LCR N do not. In HeLa cells, EWS is less O -GlcNAcylated following OGT knockdown, which correlates with its increased accumulation in a filter retardation assay. Relative to the human proteome, O -GlcNAcylated proteins are enriched with regions that are predicted to phase separate, suggesting a general role of O -GlcNAcylation in regulation of biomolecular condensates.

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 head0.021
GPT teacher head0.319
Teacher spread0.298 · 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

Citations58
Published2021
Admission routes2
Has abstractyes

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