Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA.

Paraspeckles modulate the intranuclear distribution of paraspeckle-associated Ctn RNA.
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DOI:
10.1038/srep34043
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发表时间:
2016-09-26
期刊:
影响因子:
4.6
通讯作者:
Prasanth KV
Prasanth KV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Anantharaman A;Jadaliha M;Tripathi V;Nakagawa S;Hirose T;Jantsch MF;Prasanth SG;Prasanth KV

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Paraspeckles 是由长非编码 RNA Neat1 成核的亚核结构域。虽然副斑点和 Neat1 的蛋白质成分之间的相互作用已被了解,但有关非结构 RNA 成分与副斑点的相互作用的信息有限。在这里,通过改变副斑点数量和大小,我们研究了副斑点如何影响其非结构 RNA 成分 Ctn RNA 的核组织。我们的结果表明,在没有完整副斑点的情况下,Ctn RNA 仍然保留在核中,这表明它们不调节 Ctn RNA 的核保留。在 Neat1 缺失的情况下,Ctn RNA 继续与副斑蛋白 NonO 相互作用,形成残留的核灶。此外,在不存在 Neat1 有核 paraspeckles 的情况下,Ctn RNA 的一个子集定位于核仁周围区域。随着副斑点数量的增加,转录再激活导致副斑点定位的 Ctn RNA 焦点数量增加。与 Neat1 类似,蛋白酶体抑制改变了 Ctn RNA 的定位,从而形成扩大的副斑点样病灶。超分辨率结构照明显微镜分析表明,在副斑点中,Ctn RNA 与 Neat1 部分共定位,并表现出更加异质的副斑点内定位。总的来说,这些结果表明,虽然 paraspeckles 不影响 Ctn RNA 的核保留,但它们调节其核内区室化。
Paraspeckles are sub-nuclear domains that are nucleated by long noncoding RNA Neat1. While interaction of protein components of paraspeckles and Neat1 is understood, there is limited information on the interaction of non-structural RNA components with paraspeckles. Here, by varying paraspeckle number and size, we investigate how paraspeckles influence the nuclear organization of their non-structural RNA component Ctn RNA. Our results show that Ctn RNA remains nuclear-retained in the absence of intact paraspeckles, suggesting that they do not regulate nuclear retention of Ctn RNA. In the absence of Neat1, Ctn RNA continues to interact with paraspeckle protein NonO to form residual nuclear foci. In addition, in the absence of Neat1-nucleated paraspeckles, a subset of Ctn RNA localizes to the perinucleolar regions. Concomitant with increase in number of paraspeckles, transcriptional reactivation resulted in increased number of paraspeckle-localized Ctn RNA foci. Similar to Neat1, proteasome inhibition altered the localization of Ctn RNA, where it formed enlarged paraspeckle-like foci. Super-resolution structured illumination microscopic analyses revealed that in paraspeckles, Ctn RNA partially co-localized with Neat1, and displayed a more heterogeneous intra-paraspeckle localization. Collectively, these results show that while paraspeckles do not influence nuclear retention of Ctn RNA, they modulate its intranuclear compartmentalization.
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