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

• DOI: 10.4161/rna.26214
• Publication Date: 2013-09-11T16:02:23Z
• Authors: Kaspar Burger; Bastian Mühl; Markus Kellner; Michaela Rohrmoser; Anita Gruber-Eber; Lukas Windhager; Caroline C Friedel; Lars Dölken; Dirk Eick
• Keywords: ribosome biogenesis; Nucleophosmin; Ribonucleoside

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) nascent messenger (m)RNA labeling (4sU-tagging). Here, we show that 4sU-tagging at low ≤ 10 µM can be to measure production processing ribosomal (r)RNA. However, elevated 4sU 50 µM), which are usually mRNA experiments, inhibit 47S rRNA. The inhibition rRNA synthesis accompanied by nucleoplasmic translocation nucleolar nucleophosmin (NPM1), induction tumor suppressor p53, proliferation. We conclude metabolic triggers a stress response, might influence interpretation results. Therefore, functional ribosome biogenesis, integrity, cell cycle should addressed experiments.