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