Paraspeckles are nuclear condensates which are formed around the long non-coding RNA NEAT1. According to emerging data, paraspeckle formation is triggered by phase separation of associated RNA-binding proteins with intrinsically disordered regions, which results in an orderly arrangement of paraspeckle components along NEAT1. (useful reviews: 30355755, 33748979, 29289458, 31683819).
Formation, Composition & dynamics (Assembly and disassembly)
The precise intricacies of paraspeckle structure and function were uncovered using ultra-high-resolution microscopy and multicolor tagging of paraspeckle components (the NEAT1 RNA and paraspeckle proteins). NEAT1 transcripts create a core-shell spheroidal structure, with paraspeckle proteins (PSPs) residing in distinct levels. The subdomains of NEAT1_2 play a role in RNA stability, isoform switching, and paraspeckle assembly via a liquid-liquid phase separation (LLPS) process, according to functional dissection of NEAT1 (reviewed in 32830222).
31818879 showed that ARS2 has a suppressive role on NEAT1_2 expression and the paraspeckles formation. Knockdown of ARS2 increased the number of paraspeckles.
31636118 suggested stress granules as regulators of paraspeckles formation. This study indicates that the formation of microscopically visible SGs is essential for stress-induced paraspeckle assembly. They further identified overlapping components between SGs and paraspeckles.
Relation to human diseases
Missexpression of NEAT1, the core RNA in paraspeckles, is linked to many human diseases. The oncologic influence of NEAT1 is recorded in many cancer types (ovarian cancer 32945505, gastric cancer 31486491, 29544562, oral squamous cell carcinoma 33384238) and is adequately reviewed (28105699, 33879681, 27700225, 30717168). Moreover, the role of NEAT1 in other non-cancer diseases is also described, such as liver diseases (32745314), neurodegenerative diseases (30533572), Parkinson's disease (33325399, 31311324), amyotrophic lateral sclerosis (29859124).
31636118 purified paraspeckles and identified novel paraspeckle proteins by mass spectrometry. Nevertheless, this study recorded overlap between the proteomes of paraspeckles and stress granules.
22960638 used colocalization screening with a fluorescent protein-tagged full-length cDNA library and identified 35 paraspeckle proteins.
31636118 purified paraspeckles identified novel paraspeckle proteins by mass spectrometry. Furthermore, this study recorded overlap between the proteomes of paraspeckles and stress granules.
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Xu H, Sun X, Huang Y, Si Q, Li M. Long non‑coding RNA NEAT1 modifies cell proliferation, colony formation, apoptosis, migration and invasion via the miR‑4500/BZW1 axis in ovarian cancer. Mol Med Rep. 2020 Oct;22(4):3347-3357. doi: 10.3892/mmr.2020.11408. Epub 2020 Aug 4. PMID: 32945505; PMCID: PMC7453653.
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Zhu L, He Y, Feng G, Yu Y, Wang R, Chen N, Yuan H. Genetic variants in long non-coding RNAs UCA1 and NEAT1 were associated with the prognosis of oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2021 Sep;50(9):1131-1137. doi: 10.1016/j.ijom.2020.11.024. Epub 2020 Dec 29. PMID: 33384238.
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Adriaens C, Marine JC. NEAT1-containing paraspeckles: Central hubs in stress response and tumor formation. Cell Cycle. 2017 Jan 17;16(2):137-138. doi: 10.1080/15384101.2016.1235847. Epub 2016 Oct 4. PMID: 27700225; PMCID: PMC5388437.
Prinz F, Kapeller A, Pichler M, Klec C. The Implications of the Long Non-Coding RNA NEAT1 in Non-Cancerous Diseases. Int J Mol Sci. 2019 Feb 1;20(3):627. doi: 10.3390/ijms20030627. PMID: 30717168; PMCID: PMC6387324.
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An H, Williams NG, Shelkovnikova TA. NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found? Noncoding RNA Res. 2018 Nov 15;3(4):243-252. doi: 10.1016/j.ncrna.2018.11.003. Erratum in: Noncoding RNA Res. 2020 Nov 07;5(4):219. PMID: 30533572; PMCID: PMC6257911.
Boros FA, Vécsei L, Klivényi P. NEAT1 on the Field of Parkinson's Disease: Offense, Defense, or a Player on the Bench? J Parkinsons Dis. 2021;11(1):123-138. doi: 10.3233/JPD-202374. PMID: 33325399; PMCID: PMC7990444.
Simchovitz A, Hanan M, Niederhoffer N, Madrer N, Yayon N, Bennett ER, Greenberg DS, Kadener S, Soreq H. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. FASEB J. 2019 Oct;33(10):11223-11234. doi: 10.1096/fj.201900830R. Epub 2019 Jul 17. PMID: 31311324; PMCID: PMC6766647.
Shelkovnikova TA, Kukharsky MS, An H, Dimasi P, Alexeeva S, Shabir O, Heath PR, Buchman VL. Protective paraspeckle hyper-assembly downstream of TDP-43 loss of function in amyotrophic lateral sclerosis. Mol Neurodegener. 2018 Jun 1;13(1):30. doi: 10.1186/s13024-018-0263-7. PMID: 29859124; PMCID: PMC5984788.
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