The conservation landscape of the human ribosomal RNA gene repeats

Abstract

Ribosomal RNA gene repeats (rDNA) encode ribosomal RNA, a major component of ribosomes. Ribosome biogenesis is central to cellular metabolic regulation, and several diseases are associated with rDNA dysfunction, notably cancer, However, its highly repetitive nature has severely limited characterization of the elements responsible for rDNA function. Here we make use of phylogenetic footprinting to provide a comprehensive list of novel, potentially functional elements in the human rDNA. Complete rDNA sequences for six non-human primate species were constructed using de novo whole genome assemblies. These new sequences were used to determine the conservation profile of the human rDNA, revealing 49 conserved regions in the rDNA intergenic spacer (IGS). To provide insights into the potential roles of these conserved regions, the conservation profile was integrated with functional genomics datasets. We find two major zones that contain conserved elements characterised by enrichment of transcription-associated chromatin factors, and transcription. Conservation of some IGS transcripts in the apes underpins the potential functional significance of these transcripts and the elements controlling their expression. Our results characterize the conservation landscape of the human IGS and suggest that noncoding transcription and chromatin elements are conserved and important features of this unique genomic region.

Non-random distribution of microsatellite motifs and (TTAGGG)n repeats in the monkey frog Pithecopus rusticus (Anura, Phyllomedusidae) karyotype

“…(Adonina et al, 2015). The frequent association between microsatellite repeats and the NORs is not en-tirely unexpected, given that the massive presence of microsatellite repeats has been observed in intergenic spacers (IGSs) in the rDNA (Ruiz-Ruano et al, 2015;Agrawal and Ganley, 2018). The association between microsatellite repeats and IGS regions, in particular di-and trinucleotide motifs has been confirmed by analysis of reads combined with FISH experiments in grasshoppers (Ruiz-Ruano et al, 2015) and also corroborated in the present study.…”

Biogenesis of a Solid Condensate: Amyloid Bodies

“…The rIGS is an enigmatic region of the human genome historically, and erroneously, called the "non-transcribed region" [92]. Interestingly, in recent years, species conservation [94] and functional studies have demonstrated that these regions of the genome are transcriptionally active, known to generate noncoding RNA (ncRNA) involved in regulating rRNA expression [95][96][97][98][99][100], controlling PTBP1-regulated alternative splicing [101], and assembling A-bodies [26,27] (Fig. 3A).…”

G4 Structures in Control of Replication and Transcription of rRNA Genes

“…Among many potential reasons to become interested in genes encoding ribosomal RNA (rRNA) is the possibility to study the wide range of regulatory mechanisms used to control their expression and genomic stability. When starting from the genomic level, genes for 45S rRNA (rDNA) usually form the most abundant gene family in most eukaryotes (e.g., 150 copies per haploid genome in Saccharomyces cerevisiae , Kobayashi et al, 1998 ; 300 in human, Schmickel, 1973 ; Agrawal and Ganley, 2018 ; and 600 in Arabidopsis thaliana , Pruitt and Meyerowitz, 1986 ; Copenhaver et al, 1995 ) with a considerable individual variability in a copy number. Variability can also be seen in the lengths and nucleotide sequences of intergenic spacers separating individual transcription units of 18S-5.8S-25S transcribed by RNA Polymerase I, while the nucleotide sequences of genes coding for 18S, 5.8S and 25S rRNAs are highly conserved (reviewed in Dvorackova et al, 2015 ).…”