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Related Experiment Video

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Study of Phagolysosome Biogenesis in Live Macrophages

Study of Phagolysosome Biogenesis in Live Macrophages

Published on: March 10, 2014

Inhibiting eukaryotic ribosome biogenesis.

Dominik Awad^1,2, Michael Prattes¹, Lisa Kofler¹

¹Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/EG, A-8010, Graz, Austria.

|June 12, 2019

Summary

Researchers screened ~1000 substances and found 128 compounds that inhibit ribosome biogenesis. These inhibitors offer new ways to study this essential cellular process and explore its potential as a drug target.

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Area of Science:

Molecular Biology
Cell Biology
Biochemistry

Background:

Ribosome biogenesis is crucial for cell growth, involving over 250 essential assembly factors in eukaryotes.
Few chemical inhibitors of ribosome biogenesis are known, limiting research into this dynamic process.
Inhibiting ribosome biogenesis is a potential strategy against rapidly proliferating cells in tumors and infections.

Purpose of the Study:

To systematically identify chemical inhibitors of ribosome biogenesis.
To provide tools for studying individual maturation steps within ribosome biogenesis.
To explore ribosome biogenesis as a druggable target.

Main Methods:

A microscopy-based screen was employed to assess ribosomal subunit export defects.
~1000 chemical substances were screened for inhibitory effects.
Northern blot analysis was used to characterize rRNA processing defects.

Main Results:

128 compounds were identified that inhibit ribosome biogenesis.
Inhibitors affected maturation of either the small or large ribosomal subunit, or both.
The identified inhibitors caused diverse rRNA processing defects.

Conclusions:

The identified compounds impact various ribosome biogenesis maturation steps.
This study provides a comprehensive set of inhibitors for studying ribosome biogenesis.
Ribosome biogenesis is confirmed as a promising druggable pathway for chemical intervention.