Chromatin loops and causality loops: the influence of RNA upon spatial nuclear architecture

Abstract

An intrinsic and essential trait exhibited by cells is the properly coordinated and integrated regulation of an astoundingly large number of simultaneous molecular decisions and reactions to maintain biochemical homeostasis. This is especially true inside the cell nucleus, where the recognition of DNA and RNA by a vast range of nucleic acid-interacting proteins organizes gene expression patterns. However, this dynamic system is not regulated by simple "on" or "off" signals. Instead, transcription factor and RNA polymerase recruitment to DNA are influenced by the local chromatin and epigenetic environment, a gene's relative position within the nucleus and the action of noncoding RNAs. In addition, major phase-separated structural features of the nucleus, such as nucleoli and paraspeckles, assemble in direct response to specific transcriptional activities and, in turn, influence global genomic function. Currently, the interpretation of these data is trapped in a causality dilemma reminiscent of the "chicken and the egg" paradox as it is unclear whether changes in nuclear architecture promote RNA function or vice versa. Here, we review recent advances that suggest a complex and interdependent interaction network between gene expression, chromatin topology, and noncoding RNA function. We also discuss the functional links between these essential nuclear processes from the nanoscale (gene looping) to the macroscale (sub-nuclear gene positioning and nuclear body function) and briefly highlight some of the challenges that researchers may encounter when studying these phenomena.

Centric Fusions behind the Karyotype Evolution of Neotropical Nannostomus Pencilfishes (Characiforme, Lebiasinidae): First Insights from a Molecular Cytogenetic Perspective

“…From the cytogenetic standpoint only, certain repetitive DNA markers, including 5S and 18S rDNA, have been formerly found to be involved in the formation of centric fusions (e.g., [39][40][41]). In the case of rDNAs, this may be possibly linked with the susceptibility of these tandemly repeated clusters to double-stranded DNA breaks, perhaps resulting from (1) a frequent rRNA transcription and thus break-prone R-loop emergence, (2) intermingling of NOR (Nuclear Organizer Region)-bearing chromosomes in the interphase nucleus, or (3) possible association of rDNA-bearing sites during the meiotic prophase I [42][43][44][45][46][47][48]. With a few exceptions, the terminal position of the 18S rDNA loci on chromosomes appears to be a common feature for all Lebiasinidae genera analyzed up to now (i.e., Nannostomus, Pyrrhulina, Lebiasina, and Copeina) ( [19][20][21][22], this study).…”

Epigenetic Regulation by lncRNAs: An Overview Focused on UCA1 in Colorectal Cancer

“…Genomic DNA is packed in the nucleus into a higher order genome organization, which has a dynamic and spatial architecture. Within the nucleus, the nucleoli and paraspeckles display a unique morphology, positioning, and are related to transcriptional activity (review by References [ 21 , 22 ]). The lncRNAs, NEAT1 and MALAT1, were shown to play a role in the forming and organization of these nuclear speckle bodies.…”

Non-Coding RNA as Novel Players in the Pathophysiology of Schizophrenia

“…Long non-coding RNA represents the majority of the non-coding transcriptome and use several mechanisms to mediate their activity. Amongst their modes of action, lncRNAs are involved in regulating transcription through the inhibition or recruitment of transcription factors [ 97 , 98 ], by controlling alternate splicing of the mRNA transcript [ 99 ], by interacting with chromatin to affect the DNA structure and epigenetic state [ 100 , 101 ], and by affecting the translation and stability of mRNA via binding to complementary transcripts or removing miRNA [ 99 , 102 , 103 ] ( Figure 2 ).…”