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Integrative profiling of condensation-prone RNAs during early development.

Tajda Klobučar1, Jona Novljan2, Ira A Iosub3

  • 1National Institute of Chemistry, Ljubljana, Slovenia; The Francis Crick Institute, London, UK; PhD Program "Biosciences", Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.

Cell Genomics
|November 20, 2025
PubMed
Summary

Researchers discovered a new class of RNA molecules, termed smOOPs (semi-extractable, orthogonal-organic-phase-separation-enriched RNAs), that are crucial for forming biomolecular condensates. These RNAs have unique sequence features and interact with proteins, influencing cellular organization.

Keywords:
OOPSRIC-seqRNA-RNA interactionsRNA-protein networkscondensationcondensation-prone RNAsdeep learningphase separationsemi-extractability

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Biomolecular condensates are essential cellular structures formed by RNA-protein networks.
  • The specific RNA features driving condensate formation are not fully understood.
  • Understanding these features is key to deciphering cellular organization and function.

Purpose of the Study:

  • To identify and characterize novel classes of RNA involved in biomolecular condensate formation.
  • To elucidate the sequence and structural properties of these condensation-prone RNAs.
  • To explore the interplay between RNA characteristics and protein interactions in phase separation.

Main Methods:

  • Utilized tailored transcriptomics assays to discover and isolate specific RNA populations.
  • Employed an explainable deep learning framework to analyze RNA sequence composition and properties.
  • Investigated RNA localization, subnetwork density, and RNA-binding protein (RBP) interactions.

Main Results:

  • Identified a novel class of developmental condensation-prone RNAs termed "smOOPs" (semi-extractable, orthogonal-organic-phase-separation-enriched RNAs).
  • smOOPs exhibit distinct sequence compositions, including lower complexity and increased intramolecular folding.
  • These RNAs are enriched in larger intracellular foci, form denser RNA subnetworks, and are heavily bound by RBPs.
  • smOOPs encode proteins with intrinsically disordered regions, suggesting a combined RNA- and protein-driven phase separation mechanism.

Conclusions:

  • smOOPs represent a distinct class of RNAs critical for biomolecular condensate formation.
  • RNA sequence and structure play a significant role in driving phase separation, alongside protein components.
  • This discovery provides a foundation for further research into RNA-driven condensation principles and cellular organization.