31 January 2025 Ribosomes team up in difficult situations, new technology show Back to news 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. 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. The video below shows RNAs being translated by ribosomes. They get brighter over time, showing active 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 Marvin Tanenbaum is group leader at the Hubrecht Institute, professor of Gene Expression Dynamics at TU Delft and Investigator at Oncode Institute.
