# Deletions in (CCCT)n repeat regions belonging to the human pRNA gene inhibit its expression

## TL;DR

This study shows that deletions in specific DNA repeat regions reduce the expression of a gene important for ribosomal RNA production.

## Contribution

The study identifies specific DNA sequence variations that inhibit pRNA gene expression and promote ribosomal RNA production.

## Key findings

- SNVs and deletions in (CCCT)n repeats are more frequent in DNA than in RNA transcripts.
- DNA variants inhibit pRNA expression and indirectly promote ribosomal RNA production.
- (CCCT)n/(GGGA)n DNA repeats may form triplex structures that facilitate pRNA function.

## Abstract

Ribosomal DNA (rDNA), the most abundantly expressed locus in the human genome, is represented by hundreds of units per cell. Each unit includes a 13 kb long region (47S rDNA) containing the genes of ribosomal particles, and a 30 kb long intergenic spacer (IGS). The 47S rDNA is transcribed with varying intensity in different units, some of which remain permanently silent. A key intermediator of this silencing is the promoter-associated RNA (pRNA) produced from a 2 kb long gene situated upstream of the rDNA transcription start site. Recent studies, including ours, suggest that the sequence variability, which normally occurs in mammalian cells, may account for the selective transcription of different rDNA units. The present work is based on the deep sequencing of a pRNA gene fragment and its RNA product and subsequent bioinformatic analysis.

We found that a certain SNV, which converts the CCC motif into CCT, as well as deletions which reduce the number of (CCCT) tandem repeats, were significantly more frequent in the DNA than in the respective transcripts.

These findings allowed us to establish directly the inhibitory effect of DNA variants on the expression of pRNA and thus (indirectly) the promoting effect on the production of ribosomal RNA. Our results also suggest that (CCCT)n/(GGGA)n DNA repeats and the respective (GGGA)n RNA repeats may form triplex structures, facilitating the function of pRNA.