title: tmRNA and associated ligands: a puzzling relationship.
abstract: Translation is an efficient and accurate mechanism, needing thorough systems of control-quality to ensure the correspondence between the information carried by the messenger RNA (mRNA) and the newly synthesized protein. Among them, trans-translation ensures delivering of stalled ribosomes when translation occurs on truncated mRNAs in bacteria, followed by the degradation of the incomplete nascent proteins. This process requires transfer-messenger RNA (tmRNA), an original molecule acting as both a tRNA and an mRNA. tmRNA first enters the decoding site of stuck ribosomes and, despite the lack of any codon-anticodon interaction, acts as a tRNA by transferring its alanine to the incomplete protein. Translation then switches to a small internal coding sequence (mRNA domain), which encodes a tag directing the incomplete protein towards degradation. Although playing a central role during trans-translation, tmRNA function depends on associated proteins. Genetic, biochemical and recent structural data are starting to unravel how the process takes place, by involving three main protein partners. Small protein B (SmpB) interacts with the tRNA-like domain (TLD) of tmRNA and is indispensable and specific to the process. Elongation factor Tu (EF-Tu) binds simultaneously the TLD and brings aminoacylated tmRNA to the ribosome, as for canonical tRNAs. Ribosomal protein S1 forms complexes with tmRNA, facilitating its recruitment by the stalled ribosomes. The chronology of events, however, is poorly understood and recent data shed light on the functions attributed to the proteins involved in trans-translation. This review focuses on the puzzling relationship that tmRNA has with these three protein ligands, putting forward trans-translation as a highly dynamical process.
authors.affiliation: Université de Rennes I, UPRES JE 2311, Inserm ESPRI, Biochimie Pharmaceutique, 2, avenue du Prof. Léon Bernard, 35043 Rennes, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Saguy
authors.forename: Reynald
authors.initials: R
authors.lastname: Gillet
authors.forename: Laurent
authors.initials: L
authors.lastname: Metzinger
authors.forename: Brice
authors.initials: B
authors.lastname: Felden
mesh_terms: D008024:Ligands; D009690:Nucleic Acid Conformation; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation
chemical_list: D008024:Ligands; D012329:RNA, Bacterial; D016601:RNA-Binding Proteins; C430328:small protein B; C096222:tmRNA; D010444:Peptide Elongation Factor Tu