Researchers from the Tanenbaum group at the Hubrecht Institute have developed a new microscopy technique to observe how ribosomes function in cells. With this method, they can monitor individual ribosomes as they convert mRNA into proteins. The researchers discovered that ribosomes help each other when encountering difficulties, a process they refer to as 'ribosome cooperativity'. This technique and the findings, published in Cell, provide insights into how proteins are made and offer other researchers a tool to better study mRNA translation.
Our DNA contains genetic information essential for our body's functions. Before our body can use this information, it is copied to mRNA, a type of messenger molecule. The mRNA carries this information to the ribosomes in the cell, which then read it and produce proteins. Proteins are crucial for various processes in the body. The transfer of genetic information to proteins is known as mRNA translation.
Watching ribosomes in action
"Sometimes, the mRNA contains sections that are challenging to translate into protein. We still don't fully understand how ribosomes manage these sections", says Maximilian Madern, one of the study's lead authors. "That's why we wanted to engineer a new imaging technology to gain a better understanding of how ribosomes carry out their jobs." This new technique enables researchers to monitor an individual ribosome over time during mRNA translation.
Using their technique, the team already gained new insights into how ribosomes function. "We observed that individual ribosomes move at slightly different speeds and sometimes pause for extended periods", explains Sora Yang, the study's second lead author. Due to their differences in speed ribosomes might collide, slowing down protein production. "Detecting these speed differences was challenging", Yang continues. "So, we teamed up with Marianne Bauer's group of computational scientists at TU Delft's Department of Bionanoscience. With their expertise, we could demonstrate that ribosomes indeed operate at different speeds."
Ribosomes getting stuck
The team also made an important discovery about ribosome collisions—where one ribosome runs into another due to a tricky RNA segment or differences in speed for example. "We found that brief collisions do not immediately trigger the cell's quality control mechanisms", states Madern. "Normally, these mechanisms would remove collided ribosomes, but they kick in only if the collision lasts several minutes."
Collisions not so bad after all
To their surprise, the researchers found that these temporary collisions could be beneficial, contrary to previous beliefs. Ribosomes appear to 'help' each other in navigating difficult-to-translate RNA sections, a phenomenon they call 'ribosome cooperativity'. "This allows ribosomes to endure short collisions on problematic RNA sections, thereby promoting continuous protein production", Madern explains.
Application
The new technology gives researchers the ability to better understand ribosome behavior on an individual level. By unraveling the dynamics of mRNA translation, researchers can gain deeper insights into cellular processes and the role of protein synthesis in health and disease.
Publication
Long-term imaging of individual ribosomes reveals ribosome cooperativity in mRNA translation. Maximilian F. Madern*, Sora Yang*, Olivier Witteveen, Jet Segeren, Marianne Bauer and Marvin E. Tanenbaum. 2025. Cell.
* co-first author
About the groupleader
Marvin Tanenbaum is group leader at the Hubrecht Institute, professor of Gene Expression Dynamics at TU Delft and Investigator at Oncode Institute.
About the Hubrecht Institute
The Hubrecht Institute is a research institute focused on developmental and stem cell biology. Because of the dynamic character of the research, the institute as a variable number of research group, around 20, that do fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences ( KNAW ), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht
