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Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as membraneless organelles

Journal Nat. Cell Biol. (2023)
Title Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as membraneless organelles
Laboratory RNA Biofunction Laboratory〈Prof. HIROSE Tetsuro〉
Abstract

Many membraneless organelles (MLOs) formed through phase separation play crucial roles in various cellular processes. Although these MLOs co-exist in cells, how they maintain their independence without coalescence or engulfment remains largely unknown. Here, we investigated the molecular mechanism by which paraspeckles with core–shell architecture scaffolded by NEAT1_2 long noncoding RNAs exist as distinct MLOs. We identified NEAT1 deletion mutants that assemble paraspeckles that are incorporated into nuclear speckles. Several paraspeckle proteins, including SFPQ, HNRNPF and BRG1, prevent this incorporation and thus contribute to the segregation of paraspeckles from nuclear speckles. Shell localization of these proteins in the paraspeckles, which is determined by NEAT1_2 long noncoding RNA domains, is required for this segregation process. Conversely, U2-related spliceosomal proteins are involved in internalizing the paraspeckles into nuclear speckles. This study shows that the paraspeckle shell composition dictates the independence of MLOs in the nucleus, providing insights into the importance of the shell in defining features and functions of MLOs.

Authors

Hiro Takakuwa (1, 2), Tomohiro Yamazaki (1), Sylvie Souquere (3), Shungo Adachi (4), Hyura Yoshino (2), Naoko Fujiwara (1), Tetsuya Yamamoto (5), Tohru Natsume (6), Shinichi Nakagawa (7), Gerard Pierron (8), Tetsuro Hirose (1, 9)

  1. Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
  2. Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
  3. UMS 3655, AMMICA, Gustave Roussy, Villejuif, France.
  4. Department of Proteomics, National Cancer Center Research Institute, Tokyo, Japan.
  5. Institute for Chemical Reaction Design and Discovery, Hokkaido University, Sapporo, Japan.
  6. Cellular and Molecular Biotechnology Research Institute, National Institute for Advanced Industrial Science and Technology, Tokyo, Japan.
  7. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  8. Centre National de la Recherche Scientifique, UMR-9196, Gustave Roussy, Villejuif, France.
  9. Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.

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