The roles of long noncoding RNAs in chromosome domains

The cell nucleus is highly organized and functionally compartmentalized. Double-stranded naked DNA is complexed with core histones and assembled into nucleosomes and chromatin, which are surrounded by nuclear domains composed of RNAs and proteins. Recently, three-dimensional views of chromosome organization beyond the level of the nucleosome have been established and are composed of several layers of chromosome domains. Only a small portion of the human genome encodes proteins; the majority is pervasively transcribed into noncoding RNAs whose functions are under intensive investigation. Importantly, the questions of how nuclear retained noncoding RNAs play roles in orchestrating the chromatin structure that have been addressed. The novel noncoding RNA clusters, Eleanors, are derived from a large chromatin domain. They accumulate at the site of their own transcription to form RNA clouds in the nucleus, and they activate gene expression in the chromatin domain. Noncoding RNAs have emerging roles in genome regulation that are integrated into the spatial organization of chromatin and the nucleus.

LncRNAs as organizers of nuclear structures


(a) Xist RNA is transcribed from one of the X chromosomes and spreads to the proximal region where it recruits repressive complexes to establish and maintain the inactive state. Xist covers the entire X chromosome, leading to a compacted inactive chromosomal domain, which is further localized to the periphery of the nucleus. (b) Firre RNA is retained at its transcription site and recruits specific genes located on different chromosomes through hnRNPU. It functions as a platform for trans‐chromosomal associations and coactivation of the genes. (c) NEAT1 RNA serves as a seed for a nuclear body, the paraspeckle, in cooperation with its component proteins. (d) TUG1 and MALAT1 RNAs promote the relocation of growth control genes in response to growth signal by selectively interacting with methylated and unmethylated Pc2 on gene promoters. (e) SRA RNA interacts with p68 to form a complex with CTCF and cohesin, and contributes to the enhancer‐blocking activity via a long‐range chromosomal interaction.

Tomita S, Abdalla MO, Fujiwara S, Yamamoto T, Iwase H, Nakao M, Saitoh N. (2016) Roles of long noncoding RNAs in chromosome domains. Wiley Interdiscip Rev RNA [Epub ahead of print]. [abstract]

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