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Review
, 40 (12), 889-896

Nuclear Bodies Built on Architectural Long Noncoding RNAs: Unifying Principles of Their Construction and Function

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Review

Nuclear Bodies Built on Architectural Long Noncoding RNAs: Unifying Principles of Their Construction and Function

Takeshi Chujo et al. Mol Cells.

Abstract

Nuclear bodies are subnuclear, spheroidal, and membraneless compartments that concentrate specific proteins and/or RNAs. They serve as sites of biogenesis, storage, and sequestration of specific RNAs, proteins, or ribonucleoprotein complexes. Recent studies reveal that a subset of nuclear bodies in various eukaryotic organisms is constructed using architectural long noncoding RNAs (arcRNAs). Here, we describe the unifying mechanistic principles of the construction and function of these bodies, especially focusing on liquid-liquid phase separation induced by architectural molecules that form multiple weakly adhesive interactions. We also discuss three possible advantages of using arcRNAs rather than architectural proteins to build the bodies: position-specificity, rapidity, and economy in sequestering nucleic acid-binding proteins. Moreover, we introduce two recently devised methods to discover novel arcRNA-constructed bodies; one that focuses on the RNase-sensitivity of these bodies, and another that focuses on "semi-extractability" of arcRNAs.

Keywords: architectural RNA; liquid-liquid phase separation; low-complexity domain; multivalency; nuclear body; prion-like domain.

Figures

Fig. 1
Fig. 1. Super-resolution image of paraspeckle nuclear bodies constructed by NEAT1_2 lncRNA
Fluorescence in-situ hybridization was performed on HeLa cells to visualize NEAT1_2 5′ and 3′ regions (shown in green) and NEAT1_2 middle region (shown in magenta). A maximum intensity projection image of one nucleus, delineated by a blue dotted line, is shown. Scale bar, 2 μm. Each paraspeckle is estimated to contain about 50 NEAT1_2 molecules in HeLa cells (Chujo et al., 2017). Three clusters of paraspeckles might correspond to the approximate locations of three NEAT1 loci on three copies of chromosome 11 in HeLa cells. 5′ and 3′ regions of NEAT1_2 are located at the “shell” of paraspeckles and the middle region is located at the “core”, as previously reported (Souquere et al., 2010; West et al., 2016).
Fig. 2
Fig. 2. Multivalency-driven phase separation of cellular bodies
Most cellular bodies are considered to be phase-separated liquid droplets. Liquid-liquid phase separation is driven by multivalent architectural molecules. Such multivalent interactions can be provided by molecules such as arcRNAs and proteins containing intrinsically disordered, low-complexity domains. Multivalent interactions include charge, dipole-dipole, cation-π, π-π, and hydrophobic interactions. These interactions are very weak and short lived, enabling protein components of most bodies to be highly dynamic, rapidly exchanging with the surrounding nucleoplasm or cytoplasm. By contrast, arcRNA stays inside a nuclear body.
Fig. 3
Fig. 3. Molecular mechanism of paraspeckle formation
NEAT1_2 transcription is coupled with the binding of specific proteins to putative RNA elements embedded in NEAT1_2 sequences. Paraspeckle assembly initiates at NEAT1_2 transcription sites, via PSPs that stabilize NEAT1_2 and/or promote interactions with other PSPs, such as several PLD-containing PSPs and SWI/SNF complexes. A high transcriptional level of NEAT1_2 promotes assembly of paraspeckle by concentrating NEAT1_2 at its transcription site. Each paraspeckle contains approximately 50 NEAT1_2 molecules that are organized in several bundles, forming a core-shell spheroidal structure.

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