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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10505022" target="_blank" >RIV/00216208:11110/25:10505022 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10505022

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VG0Lyopq0S" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VG0Lyopq0S</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40246-025-00830-w" target="_blank" >10.1186/s40246-025-00830-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Background: 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. Results: 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. Conclusions: 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Background: 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. Results: 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. Conclusions: 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Human Genomics

ISSN

1473-9542

e-ISSN

1479-7364

Svazek periodika

19

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

124

Kód UT WoS článku

001604487000002

EID výsledku v databázi Scopus

2-s2.0-105020281447