4-Thiouridine inhibits rRNA synthesis and causes a nucleolar stress response

Kaspar Burger, Bastian Mühl, Markus Kellner, Michaela Rohrmoser, Anita Gruber-Eber, Lukas Windhager, Caroline C. Friedel, Lars Dölken, Dirk Eick

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

99 Zitate (Scopus)

Abstract

High concentrations (> 100 μM) of the ribonucleoside analog 4-thiouridine (4sU) is widely used in methods for RNa analysis like photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) and nascent messenger (m)RNa labeling (4sU-tagging). here, we show that 4sU-tagging at low concentrations ≤ 10 μM can be used to measure production and processing of ribosomal (r)RNa. however, elevated concentrations of 4sU (> 50 μM), which are usually used for mRNa labeling experiments, inhibit production and processing of 47s rRNa. The inhibition of rRNa synthesis is accompanied by nucleoplasmic translocation of nucleolar nucleophosmin (NPM1), induction of the tumor suppressor p53, and inhibition of proliferation. We conclude that metabolic labeling of RNa by 4sU triggers a nucleolar stress response, which might influence the interpretation of results. Therefore, functional ribosome biogenesis, nucleolar integrity, and cell cycle should be addressed in 4sU labeling experiments.

OriginalspracheEnglisch
Seiten (von - bis)1623-1630
Seitenumfang8
FachzeitschriftRNA Biology
Jahrgang10
Ausgabenummer10
DOIs
PublikationsstatusVeröffentlicht - Okt. 2013
Extern publiziertJa

Fingerprint

Untersuchen Sie die Forschungsthemen von „4-Thiouridine inhibits rRNA synthesis and causes a nucleolar stress response“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren