Paraspeckles are constructed as block copolymer micelles.

Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid–liquid phase‐separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment‐based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA‐scaffolding biomolecular condensates with optimal sizes and structures in cells. SYNOPSIS: Paraspeckles scaffolded by NEAT1_2 lncRNAs have characteristic shapes and internal structures distinct from typical LLPS droplets. Using soft matter physics theory, this study reveals that they are built as block copolymer micelles, providing a concept that RNPs act as block copolymers. NEAT1_2 RNPs behave as block copolymer and form paraspeckles as micelles.Length of the NEAT1_2 5′ and 3′ terminal domains and transcription rate of NEAT1_2 determine the internal organization, size, number, and shape of the paraspeckle.NEAT1_2 lacking both the 5′ and 3′ terminal domains form large spherical paraspeckles via macroscopic phase separation.RNPs have the potential to form various structures as block copolymer micelles. [ABSTRACT FROM AUTHOR]