Dynamics of ribosomes and release factors during translation termination in E-coli.

Inside cells, molecular machines called ribosomes make proteins using messenger RNA as a template. However, the template contains more than just the information needed to create the protein. A ‘stop codon’ in the mRNA marks where the ribosome should stop. When this is reached a group of proteins called release factors removes the newly made protein from the ribosome. Bacteria typically have three types of release factors. RF1 and RF2 recognize the stop codon, and RF3 helps to release RF1 or RF2 from the ribosome so that it can be recycled to produce another protein. It was not fully understood how the release factors interact with the ribosome and how this terminates protein synthesis. Adio et al. used TIRF microscopy to study individual ribosomes from the commonly studied bacteria species Escherichia coli. This technique allows researchers to monitor movements of the ribosome and record how release factors bind to it. The results of the experiments performed by Adio et al. show that although RF1 and RF2 are very similar to each other, they interact with the ribosome in different ways. In addition, only RF1 relies upon RF3 to release it from the ribosome; RF2 can release itself. RF3 releases RF1 by forcing the ribosome to change shape. RF3 then uses energy produced by the breakdown of a molecule called GTP to help release itself from the ribosome. Most importantly, the findings presented by Adio et al. highlight that the movements of ribosomes and release factors during termination are only loosely coupled rather than occur in a set order. Other molecular machines are likely to work in a similar way. The results could also help us to understand the molecular basis of several human diseases, such as Duchenne muscular dystrophy and cystic fibrosis, that result from ribosomes not recognizing stop codons in the mRNA.