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SHR Neuro Cancer Cardio Lipid Metab Microb

Pertschy, B; Zisser, G; Schein, H; Köffel, R; Rauch, G; Grillitsch, K; Morgenstern, C; Durchschlag, M; Högenauer, G; Bergler, H.
Diazaborine treatment of yeast cells inhibits maturation of the 60S ribosomal subunit.
Mol Cell Biol. 2004; 24(14):6476-6487 Doi: 10.1128/MCB.24.14.6476-6487.2004 [OPEN ACCESS]
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Co-authors Med Uni Graz
Köffel René
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Abstract:
Diazaborine treatment of yeast cells was shown previously to cause accumulation of aberrant, 3'-elongated mRNAs. Here we demonstrate that the drug inhibits maturation of rRNAs for the large ribosomal subunit. Pulse-chase analyses showed that the processing of the 27S pre-rRNA to consecutive species was blocked in the drug-treated wild-type strain. The steady-state level of the 7S pre-rRNA was clearly reduced after short-term treatment with the inhibitor. At the same time an increase of the 35S pre-rRNA was observed. Longer incubation with the inhibitor resulted in a decrease of the 27S precursor. Primer extension assays showed that an early step in 27S pre-rRNA processing is inhibited, which results in an accumulation of the 27SA2 pre-rRNA and a strong decrease of the 27SA3, 27SB1L, and 27SB1S precursors. The rRNA processing pattern observed after diazaborine treatment resembles that reported after depletion of the RNA binding protein Nop4p/Nop77p. This protein is essential for correct pre-27S rRNA processing. Using a green fluorescent protein-Nop4 fusion, we found that diazaborine treatment causes, within minutes, a rapid redistribution of the protein from the nucleolus to the periphery of the nucleus, which provides a possible explanation for the effect of diazaborine on rRNA processing.
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