G-quadruplexes offer a conserved structural motif for NONO recruitment to NEAT1 architectural lncRNA

Abstract The long non-coding RNA NEAT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved in gene regulation. Paraspeckle assembly requires NEAT1 recruitment of the RNA-binding protein NONO, however the NEAT1 elements responsible for recruitment are unkno...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2020-07, Vol.48 (13), p.7421-7438
Main Authors: Simko, Eric A J, Liu, Honghe, Zhang, Tao, Velasquez, Adan, Teli, Shraddha, Haeusler, Aaron R, Wang, Jiou
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Conserved Sequence
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
G-Quadruplexes
HEK293 Cells
Humans
Mice
Protein Binding
RNA and RNA-protein complexes
RNA, Long Noncoding - chemistry
RNA, Long Noncoding - metabolism
RNA-Binding Proteins - chemistry
RNA-Binding Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract The long non-coding RNA NEAT1 serves as a scaffold for the assembly of paraspeckles, membraneless nuclear organelles involved in gene regulation. Paraspeckle assembly requires NEAT1 recruitment of the RNA-binding protein NONO, however the NEAT1 elements responsible for recruitment are unknown. Herein we present evidence that previously unrecognized structural features of NEAT1 serve an important role in these interactions. Led by the initial observation that NONO preferentially binds the G-quadruplex conformation of G-rich C9orf72 repeat RNA, we find that G-quadruplex motifs are abundant and conserved features of NEAT1. Furthermore, we determine that NONO binds NEAT1 G-quadruplexes with structural specificity and provide evidence that G-quadruplex motifs mediate NONO-NEAT1 association, with NONO binding sites on NEAT1 corresponding largely to G-quadruplex motifs, and treatment with a G-quadruplex-disrupting small molecule causing dissociation of native NONO-NEAT1 complexes. Together, these findings position G-quadruplexes as a primary candidate for the NONO-recruiting elements of NEAT1 and provide a framework for further investigation into the role of G-quadruplexes in paraspeckle formation and function.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkaa475