The conservation landscape of the human ribosomal RNA gene repeats [article]

Saumya Agrawal, Austen R.D. Ganley
2018 bioRxiv   pre-print
Ribosomal RNA gene repeats (rDNA) encode ribosomal RNA, a major component of ribosomes. Ribosome biogenesis is at the forefront of cellular metabolic regulation, and consequently a number of diseases are associated with rDNA dysfunction, notably cancer, which is frequently associated with increased rRNA transcription. In addition, the rDNA has other extra-coding functions, such as roles in cell cycle regulation. However, the highly repetitive nature of the rDNA has severely limited genetic
more » ... cterization of these roles. Results: Here we make use of phylogenetic footprinting to provide a comprehensive list of potential functional elements in the human rDNA. Complete rDNA sequences for six non-human primate species were constructed using de novo assemblies of publicly available genome sequence data. These new rDNA sequences were used to determine the conservation profile of the human rDNA, which revealed 49 conserved regions in the rDNA intergenic spacer (IGS). To provide insights into the roles of these conserved regions, the conservation profile was integrated with functional genomics datasets. We find pervasive transcription of the IGS, and highlight two major zones that contain conserved elements characterised by enrichment of transcription-associated chromatin factors. Conservation of some of these noncoding IGS transcripts in the apes underpins their potential functional significance, as well as that of the elements that control their expression. Conclusions: Our results characterize the potential functional landscape of the human IGS, and suggest that noncoding transcription and chromatin structure elements are conserved and important features of this unique part of the genome.
doi:10.1101/242602 fatcat:jvmpf7wcande7aoijjgzr5x4ui