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Updated: Jun 26, 2026
06:58
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
Direct link between RACK1 function and localization at the ribosome in vivo
Scott M Coyle1, Wendy V Gilbert, Jennifer A Doudna
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Molecular and Cellular Biology
|December 31, 2008
Summary
Receptor for activated C-kinase (RACK1) functions from ribosomes, linking cell signaling to protein synthesis. Mutations affecting RACK1-ribosome binding impact drug sensitivity and mRNA binding protein association.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Receptor for activated C-kinase (RACK1) is a conserved protein involved in various signaling pathways.
- RACK1 is a stoichiometric component of eukaryotic ribosomes, specifically on the 40S ribosomal subunit.
Purpose of the Study:
- To investigate the hypothesis that RACK1's ribosome association is crucial for its in vivo function.
- To elucidate the structural basis of RACK1-ribosome interaction and its functional consequences.
Main Methods:
- Determined the 2.1-Å crystal structure of Saccharomyces cerevisiae RACK1 (Asc1p).
- Designed and analyzed eight mutant versions of RACK1 to assess ribosome binding and in vivo function.
- Assessed phenotypes of RACK1 mutants, including drug sensitivity and association of mRNA binding proteins.
Main Results:
- Identified conserved charged amino acids critical for RACK1's 40S subunit binding affinity.
- Demonstrated that yeast mutations impairing ribosome binding mimic RACK1 deletion phenotypes.
- Showed that disruption of RACK1's ribosomal position prevents Scp160 association with translating ribosomes.
Conclusions:
- Provided direct evidence that RACK1 functions from the ribosome.
- Established a physical link between the eukaryotic ribosome and cell signaling pathways.
- Highlighted the importance of RACK1-ribosome interaction for cellular processes like translation and drug response.
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