title: Defining the pathway of cytoplasmic maturation of the 60S ribosomal subunit.
abstract: In eukaryotic cells the final maturation of ribosomes occurs in the cytoplasm, where trans-acting factors are removed and critical ribosomal proteins are added for functionality. Here, we have carried out a comprehensive analysis of cytoplasmic maturation, ordering the known steps into a coherent pathway. Maturation is initiated by the ATPase Drg1. Downstream, assembly of the ribosome stalk is essential for the release of Tif6. The stalk recruits GTPases during translation. Because the GTPase Efl1, which is required for the release of Tif6, resembles the translation elongation factor eEF2, we suggest that assembly of the stalk recruits Efl1, triggering a step in 60S biogenesis that mimics aspects of translocation. Efl1 could thereby provide a mechanism to functionally check the nascent subunit. Finally, the release of Tif6 is a prerequisite for the release of the nuclear export adaptor Nmd3. Establishing this pathway provides an important conceptual framework for understanding ribosome maturation.
authors.affiliation: Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Lo
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.forename: Cyril
authors.initials: C
authors.lastname: Bussiere
authors.forename: Stefan
authors.initials: S
authors.lastname: Bresson
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
authors.forename: Arlen W
authors.initials: AW
authors.lastname: Johnson
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D054683:Ribosome Subunits, Large, Eukaryotic / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C117894:NMD3 protein, S cerevisiae; C475570:NMD3 protein, human; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C491609:TIF6 protein, S cerevisiae; C078418:developmentally regulated GTP-binding protein; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C520003:RIA1 protein, S cerevisiae; C463962:AFG2 protein, S cerevisiae