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Cited by 594

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation

Open access
Yamazaki, Tomohiro, Souquere, Sylvie, Chujo, Takeshi, Kobelke, Simon, Chong, Yee Seng, Fox, Archa H., Bond, Charles S., Nakagawa, Shinichi, Pierron, Gerard, Hirose, Tetsuro·2018·Molecular Cell

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.

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Metadata

Authors
Yamazaki, T., Souquere, S., Chujo, T., Kobelke, S., Chong, Y. S., Fox, A. H., Bond, C. S., Nakagawa, S., Pierron, G., & Hirose, T.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2018-06
Volume
70
Issue
6
Pages
1038-1053.e7
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2808919170
Cited by
594
References
42
FWCI
18.99
Type
journal article
Language
en
Open access
bronze

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Yamazaki, T., Souquere, S., Chujo, T., Kobelke, S., Chong, Y. S., Fox, A. H., Bond, C. S., Nakagawa, S., Pierron, G., & Hirose, T. (2018). Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.05.019

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