Ribosomes—the tiny factories that build proteins in our cells—don't all work with the same efficiency. Researchers from Japan have discovered that ribosomes actually compete with one another, and those that perform poorly are selectively broken down when more efficient ones are present. This built-in "survival of the fittest" mechanism keeps protein synthesis accurate and efficient, shedding new light on how cells maintain quality control and prevent ribosome-related diseases.
Inside every cell, ribosomes act as tiny but vital factories that build proteins, translating genetic information into the molecules that sustain life. Although ribosomes share the same basic structure, not all of them work with equal precision. Until now, scientists did not fully understand how cells detect and handle ribosomes that underperform.
Addressing this question, a team of researchers from Japan has identified a quality control mechanism that ensures only the most competent ribosomes survive. Their study, published in Nature Communications on 12 December 2025 and selected for the journal's Editors' Highlights, shows that ribosomes compete during protein synthesis. When translation is disrupted, the less efficient ribosomes are selectively broken down, while the stronger ones continue functioning.
The research team includes Assistant Professor Sihan Li from the Division of RNA and Gene Regulation, The Institute of Medical Science, The University of Tokyo, and the Graduate School of Pharmaceutical Sciences, Tohoku University; Dr. Okuto Shounai, Dr. Misaki Kato, and Dr. Ken Ikeuchi from the Graduate School of Pharmaceutical Sciences, Tohoku University (with Ikeuchi also affiliated with the Frontier Research Institute for Interdisciplinary Sciences and the Institute of Multidisciplinary Research for Advanced Materials, Tohoku University); and Professor Toshifumi Inada from The Institute of Medical Science, The University of Tokyo.
Using biochemical and genetic analyses in yeast, the researchers examined how ribosomes behave when translation is disrupted. The team engineered cells to contain a functional but suboptimal ribosome variant. These slower-moving ribosomes are overtaken on messenger RNA by faster, native ribosomes, causing the two types to collide. Such ribosome-ribosome collisions activate a ubiquitination-dependent quality control pathway that selectively removes the less efficient ribosomes.
"Our study introduces the concept of ribosome competition, showing that even functional but slower ribosomes are selectively degraded when more capable ones are available," explains Dr. Li, who led the research. "It is fascinating to see how cells apply a principle similar to survival of the fittest at the molecular level."
The team also explored how external factors, such as the anticancer drug cisplatin affect this process. Cisplatin, known for binding to RNA and DNA, was found to increase ribosome collisions, which in turn promoted ribosome degradation. This insight could improve understanding of how the drug acts inside cells and why it sometimes causes side effects.
"Ribosome collisions act like a cellular warning signal," highlights Dr. Li. "When ribosomes bump into each other, it alerts the cell that something is wrong. The cell then removes the problematic ribosomes to maintain efficient protein production."
The implications of this discovery extend beyond basic biology. By showing how cells maintain the quality of their protein factories, the study provides a foundation for understanding disorders caused by ribosome malfunction, known as ribosomopathies. It may also open the door to new approaches for improving the safety and effectiveness of certain drugs.
In the short term, the researchers hope their work will inspire curiosity about the hidden molecular dynamics inside cells. "We hope people find it interesting that even at the microscopic level, competition drives quality and resilience," Dr. Li adds. "This discovery connects a fundamental evolutionary idea to the inner workings of our cells."
In the long term, understanding how cells detect and eliminate underperforming ribosomes could guide the development of therapies for diseases linked to translation errors. The study offers a new perspective on how living systems maintain balance, efficiency, and accuracy—qualities that ultimately sustain life itself.
Reference
Authors: Sihan Li1,2*, Okuto Shounai2, Misaki Kato2, Ken Ikeuchi2,3,4, Toshifumi Inada1,2*
Affiliations:
1Division of RNA and Gene Regulation, The Institute of Medical Science, The University of Tokyo, Japan
2Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
3Creative Interdisciplinary Research Division, Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Japan
4Division of Organic- and Bio-materials Research, Institute of Multidisciplinary Research for Advanced Materials, Japan
About The Institute of Medical Science, The University of Tokyo
The Institute of Medical Science, The University of Tokyo (IMSUT), established in 1892 as the Institute of Infectious Diseases and renamed IMSUT in 1967, is a leading research institution with a rich history spanning over 130 years. It focuses on exploring biological phenomena and disease principles to develop innovative strategies for disease prevention and treatment. IMSUT fosters a collaborative, interdisciplinary research environment and is known for its work in genomic medicine, regenerative medicine, and advanced medical approaches like gene therapy and AI in healthcare. It operates core research departments and numerous specialized centers, including the Human Genome Center and the Advanced Clinical Research Center, and is recognized as Japan's only International Joint Usage/Research Center in life sciences.
About Assistant Professor Sihan Li from The University of Tokyo
Dr. Sihan Li is an Assistant Professor at The Institute of Medical Science, The University of Tokyo. She earned her doctorate in Pharmacological Science from Tohoku University, where she also completed her undergraduate and graduate studies in pharmaceutical sciences. Her research focuses on translation, ribosome biology, RNA regulation, and cellular quality control mechanisms, particularly ribosome stagnation and decomposition. A recipient of multiple national awards, Dr. Li investigates the molecular mechanisms underlying ribosomal degradation and gene expression instability in cells.
Funding information
This work was supported by the following fundings: AMED grant JP23gm1110010, JP223fa627001 (to T.I.), JSPS KAKENHI grant JP22H00401, JP25H00007 (to T.I.), JP23K19341, JP25K18401 (to S.L.), Takeda Science Foundation (to T.I.), and the Mitsubishi Foundation (to T.I.).
