Integrative profiling of condensation-prone RNAs during early development

TL;DR

The paper identifies a new class of RNAs called smOOPs that are prone to forming condensates during early development and are closely linked to RNA-binding proteins and disordered proteins.

Contribution

The study introduces smOOPs, a novel class of condensation-prone RNAs, and reveals their unique sequence and protein features in phase separation.

Findings

smOOPs form denser RNA subnetworks and are heavily bound by RNA-binding proteins.

smOOPs have lower sequence complexity and increased intramolecular folding.

smOOPs encode proteins with intrinsically disordered regions linked to phase separation.

Abstract

Complex RNA-protein networks play a pivotal role in the formation of many types of biomolecular condensates. How RNA features contribute to condensate formation, however, remains incompletely understood. Here, we integrate tailored transcriptomics assays to identify a distinct class of developmental condensation-prone RNAs termed “smOOPs” (semi-extractable, orthogonal-organic-phase-separation-enriched RNAs). These transcripts localize to larger intracellular foci, form denser RNA subnetworks than expected, and are heavily bound by RNA-binding proteins (RBPs). Using an explainable deep learning framework, we reveal that smOOPs harbor characteristic sequence composition, with lower sequence complexity, increased intramolecular folding, and specific RBP-binding patterns. Intriguingly, these RNAs encode proteins bearing extensive intrinsically disordered regions and are highly predicted to be involved in biomolecular condensates, indicating an interplay between RNA- and protein-based features in phase separation. This work advances our understanding of condensation-prone RNAs and provides a versatile resource to further investigate RNA-driven condensation principles.

•Semi-extractability and OOPS uncover developmental condensation-prone RNAs (smOOPs)•smOOPs are in close proximity, reflected by their denser-than-expected RNA subnetworks•Multi-omic datasets link transcript features to condensation potential•smOOPs encode proteins rich in intrinsically disordered regions prone to phase separation

Semi-extractability and OOPS uncover developmental condensation-prone RNAs (smOOPs)

smOOPs are in close proximity, reflected by their denser-than-expected RNA subnetworks

Multi-omic datasets link transcript features to condensation potential

smOOPs encode proteins rich in intrinsically disordered regions prone to phase separation

This study identifies a unique class of condensation-prone RNAs (smOOPs), defined by semi-extractability and enrichment in OOPS. smOOPs form denser-than-expected RNA-RNA subnetworks, display distinct sequence features, and are strongly bound by RBPs. They encode proteins rich in intrinsically disordered regions, suggesting a coordinated RNA-protein interplay in phase separation.

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