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NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies

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Title: NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies
Authors: Hirose, Tetsuro Browse this author
Virnicchi, Giorgio Browse this author
Tanigawa, Akie Browse this author
Naganuma, Takao Browse this author
Li, Ruohan Browse this author
Kimura, Hiroshi Browse this author
Yokoi, Takahide Browse this author
Nakagawa, Shinichi Browse this author
Benard, Marianne Browse this author
Fox, Archa H. Browse this author
Pierron, Gerard Browse this author
Issue Date: 1-Jan-2014
Publisher: Amer soc cell biology
Journal Title: Molecular biology of the cell
Volume: 25
Issue: 1
Start Page: 169
End Page: 183
Publisher DOI: 10.1091/mbc.E13-09-0558
PMID: 24173718
Abstract: Paraspeckles are subnuclear structures formed around nuclear paraspeckle assembly transcript 1 (NEAT1)/MEN epsilon/beta long noncoding RNA (IncRNA). Here we show that paraspeckles become dramatically enlarged after proteasome inhibition. This enlargement is mainly caused by NEAT1 transcriptional up-regulation rather than accumulation of undegraded paraspeckle proteins. Of interest, however, using immuno-electron microscopy, we find that key paraspeckle proteins become effectively depleted from the nucleoplasm by 50% when paraspeckle assembly is enhanced, suggesting a sequestration mechanism. We also perform microarrays from NEAT1-knockdown cells and find that NEAT1 represses transcription of several genes, including the RNA-specific adenosine deaminase B2 (ADARB2) gene. In contrast, the NEAT1-binding paraspeckle protein splicing factor proline/glutamine-rich (SFPQ) is required for ADARB2 transcription. This leads us to hypothesize that ADARB2 expression is controlled by NEAT1-dependent sequestration of SFPQ. Accordingly, we find that ADARB2 expression is strongly reduced upon enhanced SFPQ sequestration by proteasome inhibition, with concomitant reduction in SFPQ binding to the ADARB2 promoter. Finally, NEAT1(-/-) fibroblasts are more sensitive to proteasome inhibition, which triggers cell death, suggesting that paraspeckles/NEAT1 attenuates the cell death pathway. These data further confirm that paraspeckles are stress-responsive nuclear bodies and provide a model in which induced NEAT1 controls target gene transcription by protein sequestration into paraspeckles.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 廣瀬 哲郎

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