A new imaging technique reveals ribosomes work together when translating mRNA, preventing slowdowns in protein production. This discovery challenges prior beliefs and could revolutionize our understanding of cellular biology.
Scientists from the Tanenbaum group at the Hubrecht Institute have developed an advanced microscopy technique to observe ribosomes in action inside living cells. This method allows researchers to track individual ribosomes as they translate mRNA into proteins.
Their study uncovered a surprising phenomenon: ribosomes assist each other when they encounter obstacles, a process they call ‘ribosome cooperativity’. These findings, published today (January 31) in the journal Cell, provide new insights into protein synthesis and offer scientists a powerful tool to study mRNA translation more closely.
DNA carries the genetic instructions needed for our bodies to function. Before these instructions can be used, they are copied into mRNA (messenger RNA), which acts as a blueprint. Ribosomes read this blueprint and build proteins — molecules essential for countless biological processes. The conversion of genetic information into proteins is called mRNA translation, a critical step in gene expression.
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.”
These spots are socRNAs being translated by ribosomes in a cell. They get brighter over time, showing active translation. The complex, which includes the socRNA and ribosome, is attached to the plasma membrane and moves slightly in 2D. Credit: Maximilian Madern, copyright Hubrecht Instituut
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.
Expanding Possibilities for Future Research
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.
Reference: “Long-term imaging of individual ribosomes reveals ribosome cooperativity in mRNA translation” by Maximilian F. Madern, Sora Yang, Olivier Witteveen, Hendrika A. Segeren, Marianne Bauer and Marvin E. Tanenbaum, 31 January 2025, Cell.
DOI: 10.1016/j.cell.2025.01.016
Marvin Tanenbaum is group leader at the Hubrecht Institute, professor of Gene Expression Dynamics at TU Delft, and Investigator at Oncode Institute.
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