Roles for Non-coding RNAs in Spatial Genome Organization

Abstract

Genetic loci are non-randomly arranged in the nucleus of the cell. This order, which is important to overall genome expression and stability, is maintained by a growing number of factors including the nuclear envelope, various genetic elements and dedicated protein complexes. Here, we review evidence supporting roles for non-coding RNAs (ncRNAs) in the regulation of spatial genome organization and its impact on gene expression and cell survival. Specifically, we discuss how ncRNAs from single-copy and repetitive DNA loci contribute to spatial genome organization by impacting perinuclear chromosome tethering, major nuclear compartments, chromatin looping, and various chromosomal structures. Overall, our analysis of the literature highlights central functions for ncRNAs and their transcription in the modulation of spatial genome organization with connections to human health and disease.

Emerging Roles of Repetitive and Repeat-Containing RNA in Nuclear and Chromatin Organization and Gene Expression

“…Due to recent excellent reviews on the topic of lncRNA and RNA in general nuclear organization ( Creamer and Lawrence, 2017 ; Khosraviani et al, 2019 ; Michieletto and Gilbert, 2019 ; Thakur et al, 2019 ), this review will focus on the emerging evidence of the role of repetitive RNA and repeat-containing repetitive motifs (i.e., genomic, simple/tandem containing repeats) in the organization of chromatin and the regulation of gene expression.…”

“…Nuclear RNAs and in particular, lncRNAs, have been shown to be involved in the formation of these sub-nuclear structures ( Khosraviani et al, 2019 ). This is because lncRNAs exhibit properties (such as secondary structures) and repetitive elements that make them potential candidates for acting as architectural elements for chromatin organization and in this role are labeled architectural RNA (arcRNA).…”

“…Regarding spatial genome organization, non-coding RNAs (ncRNAs) have particularly emerged as major regulators and can regulate transcription at the same locus ( in cis ) from where they are transcribed or elsewhere in the genome ( in trans ) ( Khosraviani et al, 2019 ). Collectively, ncRNAs can impact genome organization by modulating perinuclear chromosome tethering, the formation of major nuclear compartments, chromatin looping, and various other chromosomal structures ( Khosraviani et al, 2019 ). Remarkably, several ncRNAs from repetitive DNA loci have emerged as major players that mediate crosstalk between spatial genome organization, expression, and stability ( Caudron-Herger et al, 2015 ).…”

“…In mammalian cells, the nuclear lamina is thought to be the key organizer of the radial arrangement of chromatin in interphase nuclei, by creating a large nuclear compartment where most of the inactive chromatin clusters in the form of lamina-associated domains (LADs) ( Peric-Hupkes et al, 2010 ; Kind et al, 2015 ; Figure 4A ). LADs are typically 0.1–10 megabases, gene-poor, enriched in heterochromatin, and display low gene activity ( Guelen et al, 2008 ; Lund et al, 2014 ; Khosraviani et al, 2019 ). The association of chromatin with the nuclear lamina through LADs aids functional organization of the genome and enables a spatio-temporal regulation of replication and transcription ( Buchwalter et al, 2019 ).…”

Multi-Scale Organization of the Drosophila melanogaster Genome

“…What ensures an insulator protein at one locus on a homolog is interacting with the insulator protein that is bound to the corresponding locus on the other homolog? We know that pairing proceeds by a random walk model [104], and that non-coding RNAs help regulate genome organization [160]; therefore, perhaps a chromosome's motion and non-coding RNAs combined with the accessibility of chromatin at pairing sites will be the connection. Regardless, this is an exciting time for investigations into the organization of the genome.…”