title: Listerin-dependent nascent protein ubiquitination relies on ribosome subunit dissociation.
abstract: Quality control of defective mRNAs relies on their translation to detect the lesion. Aberrant proteins are therefore an obligate byproduct of mRNA surveillance and must be degraded to avoid disrupting protein homeostasis. These defective translation products are thought to be ubiquitinated at the ribosome, but the mechanism of ubiquitin ligase selectivity for these ribosomes is not clear. Here, we in vitro reconstitute ubiquitination of nascent proteins produced from aberrant mRNAs. Stalled 80S ribosome-nascent chain complexes are dissociated by the ribosome recycling factors Hbs1/Pelota/ABCE1 to a unique 60S-nascent chain-tRNA complex. The ubiquitin ligase Listerin preferentially recognizes 60S-nascent chains and triggers efficient nascent chain ubiquitination. Interfering with Hbs1 function stabilizes 80S complexes, precludes efficient Listerin recruitment, and reduces nascent chain ubiquitination. Thus, ribosome recycling factors control Listerin localization, explaining how translation products of mRNA surveillance are efficiently ubiquitinated while sparing translating ribosomes.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Sichen
authors.initials: S
authors.lastname: Shao
authors.forename: Karina
authors.initials: K
authors.lastname: von der Malsburg
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D002474:Cell-Free System; D004720:Endonucleases; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D008840:Microfilament Proteins; D009687:Nuclear Proteins; D012343:RNA, Transfer; C539338:Ltn1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D004720:Endonucleases; C550527:pelo protein, human; D020558:GTP Phosphohydrolases