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USP21 and OTUD3 Antagonize Regulatory Ribosomal Ubiquitylation and Ribosome‐associated Quality Control Pathways
Author(s) -
Garshott Danielle M.,
Leonard Marilyn,
Sundaramoorthy Elayanambi,
Bennett Eric J.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.526.29
Subject(s) - ribosome , ubiquitin ligase , ribosomal rna , ribosomal protein , microbiology and biotechnology , eukaryotic ribosome , biology , messenger rna , translation (biology) , ubiquitin , 30s , eukaryotic large ribosomal subunit , rna , biochemistry , gene
Ribosomal translation of messenger RNA into properly decoded polypeptides is a tightly‐controlled process that is regulated by a number of cellular quality control pathways. When ribosomes encounter defective mRNA or otherwise experience a terminal stall in translation, the ribosome‐associated quality control pathway is initiated. Conserved ubiquitylation events on specific 40S ribosomal proteins are required for downstream destruction of the mRNA and nascent peptide as well as recycling of ribosomal subunits. We have previously demonstrated that the E3 ubiquitin ligase, ZNF598, is responsible for regulatory ubiquitylation (RRub) at specific sites on the 40S ribosomal subunit during ribosome‐associated quality control events. Here we demonstrate that the deubiquitylating enzymes USP21 and OTUD3 directly antagonize these regulatory ribosomal ubiquitylation events, and catalyze the deubiquitylation of particular 40S ribosomal proteins. For the majority of cell types, the relative RNA expression and protein levels of ZNF598 as compared to USP21 and OTUD3 is substantially higher for the ligase, suggesting a constrained stoichiometric balance that is required to maintain cellular homeostasis. Overexpression of USP21 or OTUD3 results in enhanced read‐through of polyA sequences that would normally induce ribosomal stalling and abort translation elongation. Our results establish USP21 and OTUD3 catalyzed RRub deubiquitylation as a critical checkpoint on ribosome‐associated quality control. Support or Funding InformationThis project described was supported by Grant Number T32 ES007059 from NIH NIEHS and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or NIH. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .