Related Experiment Video
Updated: May 5, 2026
06:58
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
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Ribosome biogenesis bottlenecks reveal vulnerabilities in cancer
Lifei Jiang1, Qiwei Yu2, Sofia A Quinodoz3,4,5
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Biorxiv : the Preprint Server for Biology
|May 4, 2026
Summary
Oncogene activation boosts ribosome production but creates bottlenecks, reducing efficiency. Targeting these late-stage ribosome biogenesis defects can impair cancer cell growth and tumor development.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Biology
Background:
- Cellular growth necessitates increased protein synthesis, driven by ribosome production.
- Ribosome biogenesis is a complex pathway involving precursor ribosomal RNA (rRNA) processing and assembly into ribosomal subunits.
- Oncogene activation enhances rRNA transcription, leading to enlarged nucleoli and rapid ribosome production.
Purpose of the Study:
- To investigate whether oncogene-driven rRNA transcription is proportionally converted into mature ribosomes.
- To determine if coordination across rRNA maturation steps limits ribosome production yield.
- To identify potential therapeutic vulnerabilities in cancer related to ribosome biogenesis.
Main Methods:
- Quantitative pulse-chase sequencing to measure pre-rRNA transcription (input) and newly-assembled cytoplasmic ribosomes (output).
- Mathematical modeling to analyze rRNA maturation kinetics.
- Perturbation of late-stage ribosome biogenesis factors in cell and mouse models.
Main Results:
- Oncogene activation reduces the efficiency of ribosome production, despite increased rRNA transcription.
- Late-stage rRNA processing exhibits bottlenecks, with delayed maturation and increased degradation.
- Impairing late-stage ribosome biogenesis factors selectively hinders oncogene-driven cell growth and tumor progression.
Conclusions:
- Oncogene-driven ribosome production is imperfectly coordinated, creating late-stage bottlenecks.
- These bottlenecks represent selective vulnerabilities exploitable in cancer therapy.
- Capacity limits in multi-step biogenesis pathways offer potential therapeutic targets for cancer and other diseases.
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