title: Principles of cotranslational ubiquitination and quality control at the ribosome.
abstract: Achieving efficient cotranslational folding of complex proteomes poses a challenge for eukaryotic cells. Nascent polypeptides that emerge vectorially from the ribosome often cannot fold stably and may be susceptible to misfolding and degradation. The extent to which nascent chains are subject to cotranslational quality control and degradation remains unclear. Here, we directly and quantitatively assess cotranslational ubiquitination and identify, at a systems level, the determinants and factors governing this process. Cotranslational ubiquitination occurs at very low levels and is carried out by a complex network of E3 ubiquitin ligases. Ribosome-associated chaperones and cotranslational folding protect the majority of nascent chains from premature quality control. Nonetheless, a number of nascent chains whose intrinsic properties hinder efficient cotranslational folding remain susceptible for cotranslational ubiquitination. We find that quality control at the ribosome is achieved through a tiered system wherein nascent polypeptides have a chance to fold before becoming accessible to ubiquitination.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Duttler
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pechmann
authors.forename: Judith
authors.initials: J
authors.lastname: Frydman
mesh_terms: D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D017510:Protein Folding; D011786:Quality Control; D012333:RNA, Messenger / Q000235:genetics; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D018832:Molecular Chaperones; D010455:Peptides; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases