Non-coding RNAs in chromatin folding and nuclear organization

Abstract

One of the most intriguing questions facing modern biology concerns how the genome directs the construction of cells, tissues, and whole organisms. It is tempting to suggest that the part of the genome that does not encode proteins contains architectural plans. We are still far from understanding how these plans work at the level of building tissues and the body as a whole. However, the results of recent studies demonstrate that at the cellular level, special non-coding RNAs serve as scaffolds for the construction of various intracellular structures. The term "architectural RNAs" was proposed to designate this subset of non-coding RNAs. In this review, we discuss the role of architectural RNAs in the construction of the cell nucleus and maintenance of the three-dimensional organization of the genome.

Keywords: 3D genome; Liquid condensate; Non-coding RNA; Nucleus; Transcription.

Fig. 1

Compartmentalization of the cell nucleus. a A schematic of the cell nucleus depicting the existence of chromosome territories and interchromatin compartment (IC) harboring non-membrane nuclear bodies (liquid compartments). b A schematic view of a section of the nucleus showing chromosomal territories composed of chromatin globules. IC surrounds and permeates chromosomal territories. Transcription occurs in a perichromatin layer that lines chromatin globules and is in direct contact with the IC, which contains various nuclear bodies, nascent transcripts, and RNA–protein complexes

Fig. 2

RNA as a scaffold for the assembly of phase condensates and protein complexes. a Formation of an RNA–protein condensate on a scaffolding RNA mesh generated by pairing of RNAs containing complementary regions. Increase in the local concentration of RNA-bound proteins above a threshold level leads to phase separation. The formed condensate may retain proteins that are not directly bound to RNA. b Assembly of RNA–protein complexes on a folded RNA scaffold ensuring correct mutual positioning of interacting proteins

Fig. 3

Contribution of RNA to targeting chromatin-modifying complexes. a Association of chromatin-modifying enzymes and other proteins with nascent transcripts near the site of transcription may lead to the formation of a phase condensate, which may eventually incorporate remote genomic regions located in spatial proximity to the site of transcription that has nucleated assembly of the liquid condensate. b Delivery of a chromatin-modifying enzyme to a specific genomic site through interaction with RNA that forms RNA–DNA triplex or R-loop with the corresponding genomic site

Fig. 4

RNA supports 3D genome architecture. a Trans-chromosomal contacts mediated by lncRNA Firre. b A mechanism of RNA-assisted promoter–enhancer communication based on fusing of phase condensates formed around superenhancer and promoter with the assistance of RNA produced from superenhancer and promoter. c Preferential association of a DNA-binding protein with a subset of recognition sites in DNA modulated by association with lncRNA

Fig. 5

Methods for studying RNA–chromatin interactions at a genome-wide scale. a “One-vs-all” technologies for mapping sites of chromosomal location for one selected RNA based on the hybridization with complementary biotinylated oligonucleotides. b “All-to-all” technologies based on proximity ligation for generating genome-wide binding profiles for all RNA molecules present in the nucleus (exemplified by Red-C technique). c SPRITE, an “all-to-all” ligation-free technology based on split-pool ligation for identification of multiplex RNA–DNA interactions. d Mapping sites of RNA–chromatin interaction in vivo with RNA–DamID technique