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How non-coding RNAs shape nuclear structure to regulate gene expression

Guttman, Mitchell (2022) How non-coding RNAs shape nuclear structure to regulate gene expression. Biophysical Journal, 121 (3). 167a. ISSN 0006-3495. doi:10.1016/j.bpj.2021.11.1898.

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The nucleus is a highly organized arrangement of RNA, DNA, and protein molecules that are compartmentalized within three-dimensional (3D) structures involved in shared functional and regulatory processes. Although RNA has long been proposed to play a global role in organizing nuclear structure, exploring this role has remained a challenge because no existing methods can simultaneously measure RNA and DNA contacts within 3D structures. To address this, we developed RNA & DNA SPRITE (RD-SPRITE) to comprehensively map the spatial organization of all RNAs relative to DNA. Using this approach, we identify hundreds of ncRNAs that form high-concentration territories in spatial proximity to their transcriptional loci and show that dozens of ncRNAs guide diffusible regulatory proteins into these 3D structures. We show that many of these ncRNA-mediated compartments act to regulate RNA processing, heterochromatin assembly, and gene expression. Our results demonstrate a unique mechanism by which ncRNAs act to shape nuclear structure by forming high concentration territories immediately upon transcription, binding to diffusible regulators, and guiding them into spatial compartments to regulate a wide range of essential nuclear functions. Moreover, we discuss how ncRNAs can drive amplification of regulatory proteins in 3D space to enable robust control of gene expression.

Item Type:Article
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Guttman, Mitchell0000-0003-4748-9352
Additional Information:© 2021 Biophysical Society. Published by Elsevier Inc. Available online 11 February 2022, Version of Record 11 February 2022.
Issue or Number:3
Record Number:CaltechAUTHORS:20220422-230105510
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Official Citation:Mitchell Guttman, How non-coding RNAs shape nuclear structure to regulate gene expression, Biophysical Journal, Volume 121, Issue 3, Supplement 1, 2022, Page 167a, ISSN 0006-3495,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114437
Deposited By: Tony Diaz
Deposited On:25 Apr 2022 18:31
Last Modified:25 Apr 2022 18:31

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