Abstract

The formation of new ribosomes is a fundamental cellular process for each living cell and is tightly interwoven with cell cycle control and proliferation. Minimal disturbances of this pathway can result in ribosomopathies including an increased risk for certain cancer types. Thus, targeting ribosome biogenesis is an emerging strategy in cancer therapy. However, due to its complex nature, we are only at the beginning to understand the dynamics of the ribosome biogenesis pathway. One arising approach that will help us to embrace the tight timely cascade of events that is needed to form a new ribosome is the use of targeted chemical inhibition. However, only very few specific chemical inhibitors of the ribosome biogenesis pathway have been identified so far. Here we review our recently published screen to identify novel inhibitors of the ribosome biogenesis pathway in yeast (Awad et al., 2019, BMC Biology). These inhibitors can provide novel tools for basic research and can serve as starting-points to develop new chemotherapeutics.

Highlights

  • Ribosomes are ribonucleoprotein complexes in the MDa range and translate the genetic code into proteins

  • While the pre-40S precursor is rapidly transported into the cytoplasm, where the final maturation takes place, the pre60S particle undergoes numerous rearrangements and rRNA processing steps until it is exported into the cytoplasm for finalization

  • With the help of diazaborine, the first inhibitor of eukaryotic ribosome biogenesis, our lab previously demonstrated the tremendous potential to investigate the dynamics of ribosome biogenesis by targeted chemical inhibition

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Summary

Introduction

Ribosomes are ribonucleoprotein complexes in the MDa range and translate the genetic code into proteins. Only very few specific chemical inhibitors of the ribosome biogenesis pathway have been identified so far. We review our recently published screen to identify novel inhibitors of the ribosome biogenesis pathway in yeast (Awad et al, 2019, BMC Biology).

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