tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell

Abstract

Transfer messenger RNA (tmRNA; also known as 10Sa RNA or SsrA RNA) is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5’ end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to EF-Tu after aminoacylation and it enters the ribosome with EF-Tu and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with EF-Tu and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon–anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of AAA+ proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of non-functional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.

Linear Regression Links Transcriptomic Data and Cellular Raman Spectra

“…For example, the processing of rRNAs by snoRNAs is conserved for eukaryotes but does not exist in prokaryotes (Filipowicz and Pogaci c, 2002). Bacterial tmRNA (ssrA), which is scored at the top of the VIP list, removes truncated mRNAs from stalled ribosomes and recycles the ribosomes for further translation (Keiler et al, 1996) but is not present in the cytoplasm of eukaryotes (Himeno et al, 2014). The second highest transcript of E. coli encodes RNaseP (rnpB), which is involved in the processing of precursor tRNAs (Himeno et al, 2014).…”

Ribosome-associated protein quality control

“…This situation results in a trapped mRNA, partially synthesized nascent chain and ribosome. All these three issues are resolved by the molecule tmRNA 83–86 , an RNA with both tRNA- and mRNA-like properties. The tRNA-like domain of tmRNA encodes an alanine codon that can bind at the empty A site of the stalled ribosome and restart translation; the adjacent mRNA-like region is used to translate a short degradation tag before a stop codon is reached.…”

Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning

“…It also functions as an mRNA, as it contains a short ORF that is decoded after its incorporation into the ribosome. The tmRNA ORF encodes a signal for protein degradation, thus allowing the cell to destroy potentially toxic products of truncated mRNAs and also to recycle the stalled ribosomes (see REFS 166,167 for reviews and the database of tmRNA sequences 168 ). This system is remarkably conserved in bacteria and has been lost only in a few highly reduced genomes 169 .…”