Two studies discuss new fundamental properties of the ribosome as well as new ways to manipulate the ribosomal machinery. The studies published online this week in Nature Chemical Biology will have implications in basic cell biology and in biotechnology.

As highlighted by the recent Nobel Prize in chemistry, the ribosome is a complex assembled from a large number of proteins and RNA, and is essential in creating new proteins. One of the first steps in producing new proteins is binding of a substrate ― an amino acid linked to a specific RNA molecule ― to the ribosome. Later steps include biochemical reactions that are not performed by the ribosome itself, but are necessary to create the final form of each protein sequence.

Thomas Leyh, Ruben Gonzalez, Virginia Cornish and colleagues investigate the early steps of this process. Though current thinking indicates that amino acids have to be linked to a specific RNA to be used successfully, these authors show that this is not necessarily true: indeed, amino acids linked to the wrong RNA are still utilized in almost the same way to produce a new protein.

Hiroaki Suga and colleagues, in contrast, design a new way of using the processing reactions at the end of ribosomal function. By selecting a specific short protein sequence that is modified by two processing proteins, the researchers demonstrate a robust method to make cyclic peptides, of importance in drug discovery. These combined studies highlight both the increasing understanding of the ribosome and the many unanswered questions that remain.