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RNA 促进核内空间隔的形成。

RNA promotes the formation of spatial compartments in the nucleus.

机构信息

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Cell. 2021 Nov 11;184(23):5775-5790.e30. doi: 10.1016/j.cell.2021.10.014. Epub 2021 Nov 4.

Abstract

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.

摘要

RNA、DNA 和蛋白质分子在细胞核内的三维(3D)结构中高度组织化。尽管已经提出 RNA 在核组织中发挥作用,但探索这一点具有挑战性,因为现有方法无法测量 3D 结构内的高级 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。这些图谱揭示了与核功能的三个主要类别相关的高级 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,数百种 ncRNA 形成了整个细胞核内高浓度的区域,特定的 RNA 需要将各种调节剂招募到这些区域中,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。这些结果表明了一种机制,其中 RNA 形成高浓度区域,与可扩散调节剂结合,并引导它们进入隔室以调节重要的核功能。

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