Madern Maximilian F, Yang Sora, Witteveen Olivier, Segeren Hendrika A, Bauer Marianne, Tanenbaum Marvin E
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Technische Universiteit Delft, Van der Maasweg 9, 2629 HZ Delft, the Netherlands.
Oncode Institute, Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
Cell. 2025 Apr 3;188(7):1896-1911.e24. doi: 10.1016/j.cell.2025.01.016. Epub 2025 Jan 31.
The genetic information stored in mRNAs is decoded by ribosomes during mRNA translation. mRNAs are typically translated by multiple ribosomes simultaneously, but it is unclear whether and how the activity of different ribosomes on an mRNA is coordinated. Here, we develop an imaging approach based on stopless-ORF circular RNAs (socRNAs) to monitor translation of individual ribosomes in either monosomes or polysomes with very high resolution. Using experiments and simulations, we find that translating ribosomes frequently undergo transient collisions. However, unlike persistent collisions, such transient collisions escape detection by cellular quality control pathways. Rather, transient ribosome collisions promote productive translation by reducing ribosome pausing on problematic sequences, a process we term ribosome cooperativity. Ribosome cooperativity also reduces recycling of ribosomes by quality control pathways, thus enhancing processive translation. Together, our single-ribosome imaging approach reveals that ribosomes cooperate during translation to ensure fast and efficient translation.
在mRNA翻译过程中，核糖体对储存在mRNA中的遗传信息进行解码。mRNA通常会同时被多个核糖体翻译，但目前尚不清楚同一mRNA上不同核糖体的活性是否以及如何协调。在此，我们开发了一种基于无终止开放阅读框环状RNA（socRNAs）的成像方法，以非常高的分辨率监测单个核糖体在单体或多聚体中的翻译过程。通过实验和模拟，我们发现正在翻译的核糖体经常发生短暂碰撞。然而，与持续性碰撞不同，这种短暂碰撞会逃过细胞质量控制途径的检测。相反，短暂的核糖体碰撞通过减少核糖体在有问题序列上的停顿来促进高效翻译，我们将这一过程称为核糖体协同作用。核糖体协同作用还减少了质量控制途径对核糖体的循环利用，从而增强了持续性翻译。总之，我们的单核糖体成像方法揭示了核糖体在翻译过程中相互协作，以确保快速高效的翻译。
