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O-GlcNAcylation of intrinsically disordered regions selectively tunes RBP phase separation and function

ABSTRACT: Intrinsically disordered regions (IDRs) are central to liquid–liquid phase separation (LLPS), yet how post-translational modifications (PTMs) selectively regulate IDR-driven phase behavior remains unclear. Here, we systematically analyze PTMs across RNA-binding proteins (RBPs), a protein class highly enriched in IDRs. By integrating curated PTM databases with quantitative chemoenzymatic profiling, we find that although many RBPs are O-GlcNAc modified, only a small fraction (~5%) exhibits high-level O-GlcNAcylation. Notably, all highly modified RBPs undergo LLPS but display diverse condensate dynamics, indicating context-dependent regulation. Mechanistic analyses of representative candidates reveal that O-GlcNAcylation can exert opposing effects on LLPS depending on protein context.

ORGANISM(S): Homo Sapiens

SUBMITTER: Shixian Lin

PROVIDER: PXD073978 | iProX | Tue Feb 03 00:00:00 GMT 2026

REPOSITORIES: iProX

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