title: Ribosomal proteins produced in excess are degraded by the ubiquitin-proteasome system.
abstract: Ribosome assembly is an essential process that consumes prodigious quantities of cellular resources. Ribosomal proteins cannot be overproduced in Saccharomyces cerevisiae because the excess proteins are rapidly degraded. However, the responsible quality control (QC) mechanisms remain poorly characterized. Here we demonstrate that overexpression of multiple proteins of the small and large yeast ribosomal subunits is suppressed. Rpl26 overexpressed from a plasmid can be detected in the nucleolus and nucleoplasm, but it largely fails to assemble into ribosomes and is rapidly degraded. However, if the endogenous RPL26 loci are deleted, plasmid-encoded Rpl26 assembles into ribosomes and localizes to the cytosol. Chemical and genetic perturbation studies indicate that overexpressed ribosomal proteins are degraded by the ubiquitin-proteasome system and not by autophagy. Inhibition of the proteasome led to accumulation of multiple endogenous ribosomal proteins in insoluble aggregates, consistent with the operation of this QC mechanism in the absence of ribosomal protein overexpression. Our studies reveal that ribosomal proteins that fail to assemble into ribosomes are rapidly distinguished from their assembled counterparts and ubiquitinated and degraded within the nuclear compartment.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Sung
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Reitsma
authors.affiliation: Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sweredoski
authors.affiliation: Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hess
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125 deshaies@caltech.edu.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Deshaies
mesh_terms: D001343:Autophagy; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: D012335:RNA, Ribosomal; C489218:RPL26A protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex