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Updated: Sep 12, 2025

Author Spotlight: Developing Synthetic Cells from Programmable Amphiphilic DNA Nanostructures
Published on: May 31, 2024
Immiscible proteins compete for RNA binding to order condensate layers
Wilton T Snead1,2, Mary K Skillicorn3,4, Krishna Shrinivas3,4
1Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Nuclear paraspeckles organize via competitive RNA binding. Core proteins like FUS and NONO bind shell-associated NEAT1 RNA, challenging previous models and revealing principles of biomolecular condensate organization.
Area of Science:
- Cell Biology
- Molecular Biology
- Biophysics
Background:
- Biomolecular condensates compartmentalize cellular functions.
- Many condensates feature distinct internal subdomains.
- Understanding the rules governing condensate organization is crucial.
Purpose of the Study:
- To investigate the assembly logic of nuclear paraspeckles.
- To determine how lncRNA NEAT1 scaffolds paraspeckle subdomains.
- To elucidate the roles of FUS, NONO, and TDP-43 in paraspeckle organization.
Main Methods:
- Bioinformatics analysis of RNA-protein interactions.
- Biochemical experiments to study protein binding preferences.
- Physics-based simulations of condensate assembly.
Main Results:
- Core proteins FUS and NONO preferentially bind shell-associated NEAT1 domains, contrary to prevailing models.
- The shell protein TDP-43 forms surfactant-like layers around core protein condensates.
- Competitive RNA binding and protein immiscibility drive paraspeckle layer formation.
Conclusions:
- Paraspeckle organization is governed by competitive binding of core proteins to specific NEAT1 RNA domains.
- Subcondensate organization can emerge from a balance of collaborative and competitive interactions.
- This study redefines the understanding of lncRNA-mediated biomolecular condensate assembly.
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