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Paraspeckle

In cell biology, a paraspeckle is an irregularly shaped compartment of the cell, approximately 0.2-1 μm in size, found in the nucleus' interchromatin space. First documented in HeLa cells, where there are generally 10 to 30 per nucleus, Paraspeckles are now known to also exist in all human primary cells, transformed cell lines, and tissue sections. Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckle" refers to the splicing speckles to which they are always near. Their function is not fully understood, but they are thought to regulate gene expression by sequestrating proteins or mRNAs with inverted repeats in their 3′ UTRs.

Structure
Paraspeckles are organised into core-shell spheroidal structures; seven proteins on a scaffold of lncRNA NEAT1 (the 23kb isoform termed NEAT1_2 or NEAT1v2). become more abundant with stress, seem to function through sequestering other proteins, and both have distinct core or shell regions with predictable localised molecules. ==Localization==
Localization
Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription-dependent. All five of the proposed protein components have RNA recognition motifs (RRMs) and, in the absence of RNA polymerase II transcription, the paraspeckle disappears and all of its associated proponents form a crescent-shaped perinucleolar cap in the nucleolus. This phenomenon is demonstrated during the cell cycle. In the cell cycle, paraspeckles are present during interphase and during all of mitosis except for telophase because, when the two daughter nuclei are formed, there is no RNA Pol II transcription so the protein components instead form a perinucleolar cap. The localization patterns were also duplicated in experiments using transcription inhibiting drugs. ==Function==
Function
The role of the paraspeckle is not fully understood. It has been suggested that the activity of NONO (a.k.a. p54nrb), a protein component, is dependent on its localisation within the nucleus. Also, a meta-analysis by Fox et al. (2018) records that quantities of NEAT1 and thus paraspeckles are increased in digestive system tumours and respiratory cancers. Furthermore, that expression of NEAT1 is associated with tumour size, stage of cancer, ability to spread, and overall patient survival. While failure to regulate NEAT1 production has been linked to non-cancerous diseases, such as neurodegenerative diseases like Parkinson's or Alzheimer's. influenza, and Hantaan, as well as the DNA-encoded herpes simplex virus. Wang Z, Li K, Huang W (2019) Furthermore, Wang Z, Li K, Huang W (2019) state that NEAT1 can regulate expression by associating with RNA-binding proteins this regulates RNA splicing events and can manipulate the stability of proteins. Another form of molecule sequestering is through NONO and SFPQ, both proteins can bind to double-stranded RNA that has formed as a result of transcribed inverted repeat motifs. Another aspect of molecular function is NEAT1's localisation of paraspeckle proteins to direct their activity. In a study by Hirose, T. et al. (2014), when NEAT1_2 levels increase, paraspeckles elongate. This, in turn, not only increases paraspeckle length but also the demand for more paraspeckle proteins to build the tertiary structures required for proper functioning. This reduces nucleoplasmic protein availability. It was noted in their study that this has an impact on the role of free paraspeckle proteins such as SFPQ which normally represses IL-8, an immune-responsive gene, or can activate the ADARB2 gene. Thus, gene regulation can be manipulated not just through sequestering of non-constituent proteins but also paraspeckle constitutive proteins. ==Paraspeckle composition==
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