Two recent studies shed light onto the mechanism of stalled ribosome rescue and reveal how proteins can regulate translation by mimicking RNA. Translation of mRNAs that lack a stop codon results in ribosome stalling. Transfer-messenger RNA (tmRNA) — which contains a tRNA-like domain (TLD) that can be aminoacetylated with Ala and an mRNA-resembling open reading frame — acts in concert with SmpB and elongation factor Tu (EF-Tu) to release stalled ribosomes in bacteria. Neubauer et al. resolved the crystal structure of bacterial ribosomes bound to a fragment of tmRNA (Ala-tmRNAΔm), SmpB and EF-Tu. Interestingly, the carboxyl terminus of SmpB interacts with ribosomes downstream of the aminoacyl-tRNA binding site (A site). As this ribosomal region is occupied by mRNA in translating ribosomes, the C terminus of SmpB contributes to the specific recognition of stalled ribosomes. Moreover, the interaction of SmpB with the decoding centre of the ribosome induces domain closure of the 30S subunit, which presumably leads to the EF-Tu-mediated positioning of the TLD into the peptidyl transferase centre (PTC). This, in turn, promotes ribosome release.
YaeJ, a protein that shares similarities with the catalytic domain of polypeptide chain release factors, can rescue stalled ribosomes in a tmRNA-independent manner. Gagnon et al. resolved the crystal structure of YaeJ bound to bacterial ribosomes. The C-terminal tail of YaeJ was shown to detect stalled ribosomes also by binding to the ribosome downstream of the A site. This binding facilitates positioning of the YaeJ GGQ motif into the PTC, which can then mediate peptide release.
This is a preview of subscription content, access via your institution
