An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles.

An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles.
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DOI:
10.1016/j.molcel.2009.01.026
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发表时间:
2009-03-27
期刊:
影响因子:
16
通讯作者:
Lawrence, Jeanne B.
Lawrence, Jeanne B.
中科院分区:
生物学1区
文献类型:
--
作者:
Clemson, Christine M.;Hutchinson, John N.;Sara, Sergio A.;Ensminger, Alexander W.;Fox, Archa H.;Chess, Andrew;Lawrence, Jeanne B.

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NEAT1 RNA 是一种高度丰富的 4 kb ncRNA,保留在细胞核中约 10-20 个大病灶中,我们证明这些病灶与 paraspeckles(与 mRNA 核保留有关的核结构域)完全一致。通过 RNAi 消除 NEAT1 RNA 可以根除副斑点,这表明它控制副斑点蛋白、PSP1 和 p54(与 A-I 编辑相关的因子)的隔离。与 PSP1 的过度表达不同,NEAT1 过度表达会增加副斑点数量,并且副斑点仅从 NEAT1 转录位点产生。 PSP-1 RNA 结合域是其与副斑点中的 NEAT1 RNA 共定位所必需的,生化分析支持 NEAT1 RNA 与副斑点蛋白结合。与其他核保留 RNA 不同,NEAT1 RNA 未经 A-I 编辑,这与副斑雀中的结构作用一致。总体结果表明,NEAT1 是副斑点的重要结构决定因素,为 ncRNA 作为核结构域的基础提供了先例。
NEAT1 RNA, a highly abundant 4 kb ncRNA, is retained in nuclei in ~10–20 large foci that we show is completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear retention. Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting it controls sequestration of the paraspeckle proteins, PSP1 and p54, factors linked to A-I editing. Unlike over-expression of PSP1, NEAT1 over-expression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcription site. The PSP-1 RNA binding domain is required for its co-localization with NEAT1 RNA in paraspeckles, and biochemical analyses supports that NEAT1 RNA binds with paraspeckle proteins. Unlike other nuclear retained RNAs, NEAT1 RNA is not A-I edited, consistent with a structural role in paraspeckles. Collectively results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.
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