Molecular anatomy of the architectural NEAT1 noncoding RNA: The domains, interactors, and biogenesis pathway required to build phase‐separated nuclear paraspeckles

• Published in: Wiley interdisciplinary reviews. RNA Vol. 10; no. 6; pp. e1545 - n/a
• Main Authors: Hirose, Tetsuro, Yamazaki, Tomohiro, Nakagawa, Shinichi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-11-2019; Wiley Subscription Services, Inc
• Subjects: Anatomy; Binding sites; Biosynthesis; Introns; LLPS; Localization; long noncoding RNA; nuclear bodies; Nuclear transport; Proteins; ribonucleoprotein complex; Riboswitches; RNA transport; RNA-mediated interference; RNA‐binding protein; Transcription; LLPS; long noncoding RNA; RNA-binding protein; nuclear bodies; ribonucleoprotein complex
• ISSN: 1757-7004; 1757-7012
• DOI: 10.1002/wrna.1545

Long noncoding RNAs (lncRNAs) are extremely diverse and have various significant physiological functions. lncRNAs generally associate with specific sets of RNA‐binding proteins (RBPs) to form functional ribonucleoprotein (RNP) complexes. NEAT1 is a highly abundant lncRNA in the mammalian cell nucleus that associates with specific RBPs to form NEAT1 RNPs. Intriguingly, cellular NEAT1 RNPs are extraordinarily large and can be detected using an optical microscope. These gigantic RNPs, so‐called paraspeckles, are a type of membraneless nuclear body. Paraspeckles contain approximately 50 NEAT1 RNA molecules together with characteristic RBPs possessing aggregation‐prone prion‐like domains. Paraspeckle formation proceeds on the nascent NEAT1 transcript in conjunction with NEAT1 biogenesis, which exhibits various features that differ from those exhibited by mRNA biogenesis, including a lack of introns, noncanonical 3′ end formation, and nuclear retention. These unique features may be required for the mechanism of paraspeckle formation. NEAT1 possesses three distinct RNA domains (A, B, and C), which function in stabilization (A), isoform switching (B), and paraspeckle assembly (C). In particular, the central C domain contains smaller subdomains that are high‐affinity binding sites for the essential paraspeckle proteins (NONO and SFPQ) that subsequently polymerize along NEAT1. Subsequent recruitment of additional essential PSPs (FUS and RBM14) induces liquid–liquid phase separation to build a massive paraspeckle structure. Thus, the molecular anatomy of the NEAT1 arcRNA provides an ideal model to understand how lncRNAs form the functional RNP machinery.
This article is characterized under:
RNA Export and Localization > Nuclear Export/Import
RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
The NEAT1 architectural RNA is a structural scaffold of membraneless paraspeckle nuclear bodies. NEAT1 possesses functional RNA domains that locally concentrate prion‐like proteins to induce liquid–liquid phase separation and form paraspeckles as gigantic RNP complexes.