RNA promotes the formation of spatial compartments in the nucleus.

RNA promotes the formation of spatial compartments in the nucleus.
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DOI:
10.1016/j.cell.2021.10.014
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发表时间:
2021-11-11
期刊:
影响因子:
64.5
通讯作者:
Guttman, Mitchell
Guttman, Mitchell
中科院分区:
生物学1区
文献类型:
--
作者:
Quinodoz, Sofia A.;Jachowicz, Joanna W.;Bhat, Prashant;Ollikainen, Noah;Banerjee, Abhik K.;Goronzy, Isabel N.;Blanco, Mario R.;Chovanec, Peter;Chow, Amy;Markaki, Yolanda;Thai, Jasmine;Plath, Kathrin;Guttman, Mitchell

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RNA、DNA和蛋白质分子在细胞核中高度组织在三维(3D)结构内。虽然RNA被认为在核组织中发挥作用,但探索这一点一直具有挑战性,因为现有方法无法测量3D结构中的高阶RNA和DNA接触。为了解决这个问题,我们开发了RNA & DNA SPRITE(RD-SPRITE)来全面绘制RNA和DNA的空间组织。这些图谱揭示了与三种主要核功能相关的高阶RNA-染色质结构:RNA加工、异染色质组装和基因调控。这些数据表明,数以百计的ncRNA在整个细胞核中形成高浓度的区域,需要特定的RNA将各种调控因子招募到这些区域中,并且这些RNA可以形成长距离DNA接触,异染色质组装和基因表达。这些结果证明了一种机制,RNA形成高浓度的领土,结合到可扩散的调节剂,并引导它们进入隔室,以调节基本的核功能。绘制RNA与DNA和其他RNA的接近度,阐明了细胞非编码RNA如何作为空间组织者,控制支持受调控基因表达的过程。
RNA, DNA, and protein molecules are highly organized within three-dimensional (3D) structures in the nucleus. Although RNA has been proposed to play a role in nuclear organization, exploring this has been challenging because existing methods cannot measure higher-order RNA and DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the spatial organization of RNA and DNA. These maps reveal higher-order RNA-chromatin structures associated with three major classes of nuclear function: RNA processing, heterochromatin assembly, and gene regulation. These data demonstrate that hundreds of ncRNAs form high-concentration territories throughout the nucleus, that specific RNAs are required to recruit various regulators into these territories, and that these RNAs can shape long-range DNA contacts, heterochromatin assembly, and gene expression. These results demonstrate a mechanism where RNAs form high-concentration territories, bind to diffusible regulators, and guide them into compartments to regulate essential nuclear functions. Mapping the proximity of RNAs to DNA and to other RNAs elucidates how cellular noncoding RNAs serve as spatial organizers controlling processes underpinning regulated gene expression.
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