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)
Relation to human diseases
Proteome
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).
Proteome
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.
References
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