How to build a Protoribosome. Structural insights from the first protoribosome constructs that have proven to be catalytically active.

Abstract

The modern ribosome catalyzes all coded protein synthesis in extant organisms. It is likely that its core structure is a direct descendant from the ribosome present in the last common ancestor (LCA). Hence, its earliest origins likely predate the LCA and therefore date further back in time. Of special interest is the pseudo-symmetrical region (SymR) that lies deep within the large subunit (LSU) where the peptidyl transfer reaction takes place. It was previously proposed that two RNA oligomers, representing the P- and A-regions of extant ribosomes dimerized to create a pore-like structure, which hosted the necessary properties, that facilitate peptide bond formation. However, recent experimental studies show that this may not be the case. Instead, several RNA constructs derived exclusively from the P-region were showed to form a homodimer capable of peptide bond synthesis. This seemingly modest change in our understanding is important because it provides a deeper understanding of ribosome’s history. In practice this will change the focus of future research, which will likely increasingly examine the origins and properties of the P-region. Of special interest will be the origin issues as the homodimer would have allowed a pre-LCA ribosome that was significantly smaller than previously proposed. For the A-region the immediate issue will likely be its origin and whether it enhances ribosome performance. Here, we re-analyze the RNA/RNA interaction regions that most likely lead to SymR formation in the light of these recent findings. Further, it has been suggested that the ability of these RNA constructs to dimerize and enhance peptide bond formation is sequence dependent. We have analyzed the implications of sequence variations as parts of functional and non-functional constructs.