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Cold Spring Harbor Perspectives in... Jul 2010Paraspeckles are a relatively new class of subnuclear bodies found in the interchromatin space of mammalian cells. They are RNA-protein structures formed by the... (Review)
Review
Paraspeckles are a relatively new class of subnuclear bodies found in the interchromatin space of mammalian cells. They are RNA-protein structures formed by the interaction between a long nonprotein-coding RNA species, NEAT1/Men epsilon/beta, and members of the DBHS (Drosophila Behavior Human Splicing) family of proteins: P54NRB/NONO, PSPC1, and PSF/SFPQ. Paraspeckles are critical to the control of gene expression through the nuclear retention of RNA containing double-stranded RNA regions that have been subject to adenosine-to-inosine editing. Through this mechanism paraspeckles and their components may ultimately have a role in controlling gene expression during many cellular processes including differentiation, viral infection, and stress responses.
Topics: Cell Nucleus; Humans; Microscopy, Fluorescence; Subcellular Fractions
PubMed: 20573717
DOI: 10.1101/cshperspect.a000687 -
Essays in Biochemistry Dec 2020Paraspeckles are a type of subnuclear bodies built on the long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MEN-ε/β or VINC-1).... (Review)
Review
Paraspeckles are a type of subnuclear bodies built on the long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MEN-ε/β or VINC-1). Paraspeckles are involved in many physiological processes including cellular stress responses, cell differentiation, corpus luteum formation and cancer progression. Recently, ultra-resolution microscopy coupled with multicolor-labeling of paraspeckle components (the NEAT1 RNA and paraspeckle proteins) revealed the exquisite details of paraspeckle structure and function. NEAT1 transcripts are radially arranged to form a core-shell spheroidal structure, while paraspeckle proteins (PSPs) localize within different layers. Functional dissection of NEAT1 shows that the subdomains of NEAT1_2 are important for RNA stability, isoform switching and paraspeckle assembly via a liquid-liquid phase separation (LLPS) mechanism. We review recent progress on structure and organization of paraspeckles as well as how paraspeckles spatiotemporally control gene regulation through sequestration of diverse proteins and RNAs in cells.
Topics: Cell Nucleus; Gene Expression; Gene Expression Regulation; Humans; Protein Domains; Protein Isoforms; RNA Stability; RNA, Long Noncoding; RNA-Binding Proteins
PubMed: 32830222
DOI: 10.1042/EBC20200010 -
Nucleus (Austin, Tex.) May 2017Circadian clocks regulate rhythmic gene expression levels by means of mRNA oscillations that are mainly driven by post-transcriptional regulation. We identified a new... (Review)
Review
Circadian clocks regulate rhythmic gene expression levels by means of mRNA oscillations that are mainly driven by post-transcriptional regulation. We identified a new post-transcriptional mechanism, which involves nuclear bodies called paraspeckles. Major components of paraspeckles including the long noncoding RNA Neat1, which is the structural component, and its major protein partners, as well as the number of paraspeckles, follow a circadian pattern in pituitary cells. Paraspeckles are known to retain within the nucleus RNAs containing inverted repeats of Alu sequences. We showed that a reporter gene in which these RNA duplex elements were inserted in the 3'-UTR region displayed a circadian expression. Moreover, circadian endogenous mRNA associated with paraspeckles lost their circadian pattern when paraspeckles were disrupted. This work not only highlights a new paraspeckle-based post-transcriptional mechanism involved in circadian gene expression but also provides the list of all mRNA associated with paraspeckles in the nucleus of pituitary cells.
Topics: Animals; Cell Nucleus; Circadian Rhythm; Gene Expression Regulation; Pituitary Gland; RNA, Messenger
PubMed: 28060565
DOI: 10.1080/19491034.2016.1277304 -
Trends in Biochemical Sciences Feb 2018Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and... (Review)
Review
Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles - protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA-protein and protein-protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings.
Topics: Animals; Humans; Nuclear Proteins; Phase Transition; RNA, Long Noncoding
PubMed: 29289458
DOI: 10.1016/j.tibs.2017.12.001 -
EMBO Reports Jan 2023Paraspeckles are subnuclear RNA-protein structures that are implicated in important processes including cellular stress response, differentiation, and cancer...
Paraspeckles are subnuclear RNA-protein structures that are implicated in important processes including cellular stress response, differentiation, and cancer progression. However, it is unclear how paraspeckles impart their physiological effect at the molecular level. Through biochemical analyses, we show that paraspeckles interact with the SWI/SNF chromatin-remodeling complex. This is specifically mediated by the direct interaction of the long-non-coding RNA NEAT1 of the paraspeckles with ARID1B of the cBAF-type SWI/SNF complex. Strikingly, ARID1B depletion, in addition to resulting in loss of interaction with the SWI/SNF complex, decreases the binding of paraspeckle proteins to chromatin modifiers, transcription factors, and histones. Functionally, the loss of ARID1B and NEAT1 influences the transcription and the alternative splicing of a common set of genes. Our findings reveal that dynamic granules such as the paraspeckles may leverage the specificity of epigenetic modifiers to impart their regulatory effect, thus providing a molecular basis for their function.
Topics: Paraspeckles; Transcription Factors; RNA, Long Noncoding; Chromatin Assembly and Disassembly; Chromatin
PubMed: 36354291
DOI: 10.15252/embr.202255345 -
Non-coding RNA Oct 2020Non-coding RNA were previously thought to be biologically useless molecules arising from simple transcriptional noise. These are now known to be an integral part of... (Review)
Review
Non-coding RNA were previously thought to be biologically useless molecules arising from simple transcriptional noise. These are now known to be an integral part of cellular biology and pathology. The wide range of RNA molecules have a diverse range of structures, functions, and mechanisms of action. However, structural long non-coding RNAs (lncRNAs) are a particular class of ncRNA that are proving themselves more and more important in cellular biology, as the exact structures that such RNAs form and stabilise become more understood. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a specific structural RNA emerging as a critical component in the progress and development of cancer. NEAT1 forms part of multiple biological pathways, acting through a diverse group of mechanisms. The most important of these is the formation of the paraspeckle, through which it can influence the stability of a tumour to develop resistance to drugs. This review will thus cover the range of effects by which NEAT1 interacts with cancer progression in order to describe the various roles of NEAT1 in chemoresistance, as well as to identify drug targets that protein research alone could not provide.
PubMed: 33143162
DOI: 10.3390/ncrna6040043 -
Biology of Reproduction May 2019
Review
Topics: Animals; Cell Differentiation; Cleavage Stage, Ovum; Embryo, Mammalian; Embryonic Development; Mice; RNA, Long Noncoding; RNA-Binding Proteins
PubMed: 30721989
DOI: 10.1093/biolre/ioz021 -
Non-coding RNA Research Dec 2019The nucleus is an essential hub for the regulation of gene expression in both spatial and temporal contexts. The complexity required to manage such a feat has resulted... (Review)
Review
The nucleus is an essential hub for the regulation of gene expression in both spatial and temporal contexts. The complexity required to manage such a feat has resulted in the evolution of multiple sub-structures in the nucleus such as the nucleolus, small cajal bodies and nuclear stress bodies. The paraspeckle is another membraneless structure composed of RNA elements, primarily the long non-coding RNA (lncRNA) Nuclear Enriched Abundant Transcript 1 (NEAT1), associated with RNA binding proteins (RBPs). The paraspeckle is showing signs of being involved in various aspects of gene regulation and its role in many pathologies from cancer to viral infection is beginning to be addressed. Research into paraspeckle-directed gene regulation highlights the increase in the appreciation of the biological significance of non-coding RNA (ncRNA). This review will thus cover the basis of how a structure as large as a paraspeckle forms along with its functions. It will also explore how it effects pathological conditions and can be used in clinical intervention, with special emphasis on the multitude of methods utilised by paraspeckles for apoptotic regulation.
PubMed: 32072080
DOI: 10.1016/j.ncrna.2019.11.002 -
The EMBO Journal Jun 2021Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization,...
Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid-liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding biomolecular condensates with optimal sizes and structures in cells.
Topics: Cell Line; Humans; Micelles; Polymers; RNA, Long Noncoding; Ribonucleoproteins
PubMed: 33885174
DOI: 10.15252/embj.2020107270 -
Non-coding RNA Research Dec 2018Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical... (Review)
Review
Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experimental evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the CNS in health and disease. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is an abundant, ubiquitously expressed lncRNA, which forms a scaffold for a specific RNA granule in the nucleus, or nuclear body, the paraspeckle. Paraspeckles act as molecular hubs for cellular processes commonly affected by neurodegeneration. Transcriptomic analyses of the diseased human tissue have revealed altered NEAT1 levels in the CNS in major neurodegenerative disorders as well as in some disease models. Although it is clear that changes in NEAT1 expression (and in some cases, paraspeckle assembly) accompany neuronal damage, our understanding of NEAT1 contribution to the disease pathogenesis is still rudimentary. In this review, we have summarised the available knowledge on NEAT1 involvement in the molecular processes linked to neurodegeneration and on NEAT1 dysregulation in this type of disease, with a special focus on amyotrophic lateral sclerosis. The goal of this review is to attract the attention of researchers in the field of neurodegeneration to NEAT1 and paraspeckles.
PubMed: 30533572
DOI: 10.1016/j.ncrna.2018.11.003