Paraspeckles are constructed as block copolymer micelles

Area of Science:

• Cell Biology
• Biophysics
• RNA Biology

Background:

• Paraspeckles are nuclear bodies formed by NEAT1_2 long noncoding RNA.
• Their distinct cylindrical shape and internal organization differ from typical liquid-liquid phase-separated condensates.
• Understanding paraspeckle formation is crucial for comprehending nuclear organization and function.

Purpose of the Study:

• To experimentally and theoretically investigate the determinants of paraspeckle shape and internal organization.
• To identify specific NEAT1_2 RNA domains involved in paraspeckle structure.
• To develop a theoretical framework for paraspeckle assembly and regulation.

Main Methods:

• Experimental manipulation of NEAT1_2 RNA domains.
• Theoretical modeling using soft matter physics principles.
• Analysis of paraspeckle morphology and organization under different conditions.

Main Results:

• Specific NEAT1_2 RNA domains were identified as crucial for shell localization and internal organization.
• A theoretical framework treating paraspeckles as amphipathic block copolymer micelles successfully explained experimental observations.
• The model predicted paraspeckle behavior upon NEAT1_2 domain deletions and transcriptional changes.

Conclusions:

• Paraspeckles are proposed to assemble via micellization, acting as block copolymer micelles.
• This provides an experiment-based theoretical framework for RNA-scaffolding biomolecular condensates.
• The findings offer insights into how ribonucleoprotein complexes form structures with optimal sizes and organization in cells.