Cajal body function in genome organization and transcriptome diversity

Abstract

Nuclear bodies contribute to nonrandom organization of the human genome and nuclear function. Using a major prototypical nuclear body, the Cajal body, as an example, we suggest that these structures assemble at specific gene loci located across the genome as a result of high transcriptional activity. Subsequently, target genes are physically clustered in close proximity in Cajal body-containing cells. However, Cajal bodies are observed in only a limited number of human cell types, including neuronal and cancer cells. Ultimately, Cajal body depletion perturbs splicing kinetics by reducing target small nuclear RNA (snRNA) transcription and limiting the levels of spliceosomal snRNPs, including their modification and turnover following each round of RNA splicing. As such, Cajal bodies are capable of shaping the chromatin interaction landscape and the transcriptome by influencing spliceosome kinetics. Future studies should concentrate on characterizing the direct influence of Cajal bodies upon small nuclear RNA gene transcriptional dynamics.

Roles for Non-coding RNAs in Spatial Genome Organization

“…This is in accordance with studies reporting the loss of Cajal bodies during mitosis and their reformation during early G1 upon the resumption of transcription (Carmo-Fonseca et al, 1993;Strzelecka et al, 2010). Furthermore, these ncRNA-dependent Cajal bodies are responsible for the spatial organization and expression of other types of genes, including those encoding for histones or pre-mRNA splicing factors (Sawyer et al, 2016;Wang et al, 2016;.…”

“…Non-coding RNAs can impact the structure and function of nuclear compartments such as Cajal bodies. The latter are involved in various processes including telomerase biogenesis, 3 -end processing of histone pre-mRNAs, as well as the processing, assembly and maturation of spliceosomal small nuclear ribonucleoproteins (snRNPs) (Sawyer et al, 2016). Cajal bodies associate with small nuclear and nucleolar RNA (sn/snoRNA) gene loci, such that these genes form intra-and inter-chromosomal clusters around the bodies ( Figure 1A) (Wang et al, 2016).…”

Three-dimensional analysis of nuclear heterochromatin distribution during early development in the rabbit

“…The nucleus of a cell is divided into several membrane-less compartments such as the nucleolus or nuclear speckle (Dundr 2012) that are dedicated to specific nuclear functions (rRNA expression and processing or RNA splicing) (Dundr and Misteli 2010; Sawyer et al 2016). During the past 10 years, the involvement of nuclear architecture in the regulation of gene expression, and more particularly the spatial organization of chromatin, have been studied intensively (for a review, see Schneider and Grosschedl 2007; Joffe et al 2010; Bickmore and van Steensel 2013; Pombo and Dillon 2015; Dekker and Heard 2015).…”

Biomolecular condensates in neurodegeneration and cancer

“…Numerous condensates exist in all eukaryotic cells with unique composition, localization and function (Figure and Table ). Condensates that participate in house‐keeping functions such as ribosome biogenesis and RNA processing are constitutively present in most cell types (Figure , brown condensates) . Others assemble under certain stimuli such as proteotoxic, genotoxic or metabolic stress (Figure , red condensates) .…”