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Review
. 2020 Jul 1;6(3):26.
doi: 10.3390/ncrna6030026.

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

Affiliations
Review

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

Elisa Taiana et al. Noncoding RNA. .

Abstract

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases.

Keywords: DNA damage repair; NEAT1; cancer; lncRNA; neurodegenerative disease; paraspeckle.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the synthesis of NEAT1_1 and NEAT1_2 isoforms and PS biogenesis by the two-step process: (1) synthesis of individual NEAT1_2-Ribonucleoprotein complex with the involvement of Category 1A paraspeckle proteins (PSPs); (2) assembly of about 50 NEAT1_2-Ribonucleoprotein complexes in a final PS structure with the joining of Category 1B PSPs and member of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex (BRG1).
Figure 2
Figure 2
Schematic representation of essential PSPs belonging to category 1A and 1B and their major domains. The amino-acid length of each PSP is shown, whereas the amino-acid interval of each RNA-recognition motif (RRM), K homology RNA-binding (KH) and zinc-finger motif (ZnF) domain is indicated in red upon the corresponding region. Domain legend is shown in the box on the right.
Figure 3
Figure 3
Graphical summary of PSs cellular functions. Upper, right panel: PSs as a gene expression regulator through the A to I editing process and the consequent nuclear retention of different mRNAs. Lower, right: PSs as molecular sponges for RNA binding proteins and PSPs. Upper, left: PSs as regulator of miRNA biogenesis by regulating the assembling of the microprocessor complex involved in processing of miRNA. Lower, left: PSs as possible structural scaffold for cellular DNA damage response systems.
Figure 4
Figure 4
Schematic representation of essential PSPs involvement at different levels of DDR system.

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