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

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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.

Original languageEnglish
Pages (from-to)1623-1630
Number of pages8
JournalRNA Biology
Volume10
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • 4-Thiouridine
  • Nucleolar stress
  • Nucleophosmin
  • P53
  • RNA labeling
  • RRNA processing
  • Ribosomal RNA

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