Hokkaido University Collection of Scholarly and Academic Papers >
Institute for Genetic Medicine >
Peer-reviewed Journal Articles, etc >
Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Files in This Item:
|
|
Related Items in HUSCAP:
|
Title: | Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation |
Authors: | Yamazaki, Tomohiro Browse this author | Souquere, Sylvie Browse this author | Chujo, Takeshi Browse this author | Kobelke, Simon Browse this author | Chong, Yee Seng Browse this author | Fox, Archa H. Browse this author | Bond, Charles S. Browse this author | Nakagawa, Shinichi Browse this author →KAKEN DB | Pierron, Gerard Browse this author | Hirose, Tetsuro Browse this author →KAKEN DB |
Keywords: | noncoding RNA | architectural RNA | nuclear bodies | paraspeckle | RNA-binding proteins | prion-like domain | phase separation | 1,6-hexanediol | CRISPR/Cas9 | haploid cell |
Issue Date: | 21-Jun-2018 |
Publisher: | Cell Press |
Journal Title: | Molecular cell |
Volume: | 70 |
Issue: | 6 |
Start Page: | 1038 |
End Page: | 1053 |
Publisher DOI: | 10.1016/j.molcel.2018.05.019 |
Abstract: | A class of long noncoding RNAs (lncRNAs) has architectural functions in nuclear body construction; however, specific RNA domains dictating their architectural functions remain uninvestigated. Here, we identified the domains of the architectural NEAT1 lncRNA that construct paraspeckles. Systematic deletion of NEAT1 portions using CRISPR/Cas9 in haploid cells revealed modular domains of NEAT1 important for RNA stability, isoform switching, and paraspeckle assembly. The middle domain, containing functionally redundant subdomains, was responsible for paraspeckle assembly. Artificial tethering of the NONO protein to a NEAT1_2 mutant lacking the functional subdomains rescued paraspeckle assembly, and this required the NOPS dimerization domain of NONO. Paraspeckles exhibit phase-separated properties including susceptibility to 1,6-hexanediol treatment. RNA fragments of the NEAT1_2 subdomains preferentially bound NONO/SFPQ, leading to phase-separated aggregates in vitro. Thus, we demonstrate that the enrichment of NONO dimers on the redundant NEAT1_2 subdomains initiates construction of phase-separated paraspeckles, providing mechanistic insights into lncRNA-based nuclear body formation. |
Rights: | © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/74758 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 廣瀬 哲郎
|