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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 04, 2020
- Source ID
- 10.1093/nar/gkaa475
Entities
People
- Aaron R Haeusler
- Adan Velasquez
- Eric A J Simko
- Honghe Liu
- Jiou Wang
- Shraddha Teli
- Zhang Tao
Organizations
- Johns Hopkins University
- Muscular Dystrophy Association
- National Institutes of Health
- United States Department of Defense