Paraspeckles are constructed as block copolymer micelles

Journal EMBO J. e107270 (2021)
Title Paraspeckles are constructed as block copolymer micelles
Laboratory RNA Biofunction Laboratory〈Prof. HIROSE Tetsuro〉

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.


Tomohiro Yamazaki (1), Tetsuya Yamamoto (2), Hyura Yoshino (3), Sylvie Souquere (4), Shinichi Nakagawa (5), Gerard Pierron (6), Tetsuro Hirose (1, 3)

  1. Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
  2. Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Japan.
  3. Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
  4. UMS 3655, AMMICA, Gustave Roussy, Villejuif, France.
  5. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  6. Centre National de la Recherche Scientifique, UMR‐9196, Gustave Roussy, Villejuif, France.
PubMed 33885174