A Role for Ubiquitin in the Clearance of Nonfunctional RRNAs

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2009 Apr 25

PMID 19390089

Citations 61

Authors

Kotaro Fujii

Makoto Kitabatake

Tomoko Sakata

Atsumi Miyata

Mutsuhito Ohno

Affiliations

Soon will be listed here.

Abstract

Quality control mechanisms operate in various steps of ribosomal biogenesis to ensure the production of functional ribosome particles. It was reported previously that mature ribosome particles containing nonfunctional mutant rRNAs are also recognized and selectively removed by a cellular quality control system (nonfunctional rRNA decay [NRD]). Here, we show that the NRD of 25S rRNA requires a ubiquitin E3 ligase component Rtt101p and its associated protein Mms1p, identified previously as factors involved in DNA repair. We revealed that a group of proteins associated with nonfunctional ribosome particles are ubiquitinated in a Rtt101-Mms1-dependent manner. 25S NRD was disrupted when ubiquitination was inhibited by the overexpression of modified ubiquitin molecules, demonstrating a direct role for ubiquitin in this pathway. These results uncovered an unexpected connection between DNA repair and the quality control of rRNAs. Our findings support a model in which responses to DNA and rRNA damages are triggered by a common ubiquitin ligase complex during genotoxic stress harmful to both molecules.

Citing Articles

The integrated stress response regulates 18S nonfunctional rRNA decay in mammals.

Coria A, Shah A, Shafieinouri M, Taylor S, Orgebin E, Guiblet W Mol Cell. 2025; 85(4):787-801.e8.

PMID: 39947182 PMC: 11845294. DOI: 10.1016/j.molcel.2025.01.017.

DNA Damage Checkpoints Govern Global Gene Transcription and Exhibit Species-Specific Regulation on in .

Zhang Y, Cai H, Chen R, Feng J J Fungi (Basel). 2024; 10(6).

PMID: 38921373 PMC: 11204775. DOI: 10.3390/jof10060387.

Phenomenological interpretations of the mechanism for the concentration-dependent positive effect of antibiotic lincomycin on A3(2).

Mukai K, Shibayama T, Imai Y, Hosaka T Appl Environ Microbiol. 2023; 89(10):e0113323.

PMID: 37732750 PMC: 10617593. DOI: 10.1128/aem.01133-23.

Co-Translational Quality Control Induced by Translational Arrest.

Matsuo Y, Inada T Biomolecules. 2023; 13(2).

PMID: 36830686 PMC: 9953336. DOI: 10.3390/biom13020317.

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells.

Butler P, Pascheto I, Lizzi M, St-Onge R, Lanner C, Guo B Sci Rep. 2023; 13(1):1711.

PMID: 36720913 PMC: 9889758. DOI: 10.1038/s41598-023-28635-8.

References

Prakash L, Prakash S . Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae. Genetics. 1977; 86(1):33-55. PMC: 1213670. DOI: 10.1093/genetics/86.1.33. View

Kraft C, Deplazes A, Sohrmann M, Peter M . Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol. 2008; 10(5):602-10. DOI: 10.1038/ncb1723. View

Koc A, Wheeler L, Mathews C, Merrill G . Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools. J Biol Chem. 2003; 279(1):223-30. DOI: 10.1074/jbc.M303952200. View

Hryciw T, Tang M, Fontanie T, Xiao W . MMS1 protects against replication-dependent DNA damage in Saccharomyces cerevisiae. Mol Genet Genomics. 2002; 266(5):848-57. DOI: 10.1007/s00438-001-0605-x. View

Thompson J, Kim D, OConnor M, Lieberman K, Bayfield M, Gregory S . Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit. Proc Natl Acad Sci U S A. 2001; 98(16):9002-7. PMC: 55363. DOI: 10.1073/pnas.151257098. View

Pan X, Ye P, Yuan D, Wang X, Bader J, Boeke J . A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell. 2006; 124(5):1069-81. DOI: 10.1016/j.cell.2005.12.036. View

Krogan N, Cagney G, Yu H, Zhong G, Guo X, Ignatchenko A . Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature. 2006; 440(7084):637-43. DOI: 10.1038/nature04670. View

Isken O, Maquat L . Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev. 2007; 21(15):1833-56. DOI: 10.1101/gad.1566807. View

LaRiviere F, Cole S, Ferullo D, Moore M . A late-acting quality control process for mature eukaryotic rRNAs. Mol Cell. 2006; 24(4):619-26. DOI: 10.1016/j.molcel.2006.10.008. View

10.

Nogi Y, Yano R, Nomura M . Synthesis of large rRNAs by RNA polymerase II in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. Proc Natl Acad Sci U S A. 1991; 88(9):3962-6. PMC: 51573. DOI: 10.1073/pnas.88.9.3962. View

11.

Michel J, McCarville J, Xiong Y . A role for Saccharomyces cerevisiae Cul8 ubiquitin ligase in proper anaphase progression. J Biol Chem. 2003; 278(25):22828-37. DOI: 10.1074/jbc.M210358200. View

12.

Venema J, Tollervey D . Ribosome synthesis in Saccharomyces cerevisiae. Annu Rev Genet. 2000; 33:261-311. DOI: 10.1146/annurev.genet.33.1.261. View

13.

Rakauskaite R, Dinman J . rRNA mutants in the yeast peptidyltransferase center reveal allosteric information networks and mechanisms of drug resistance. Nucleic Acids Res. 2008; 36(5):1497-507. PMC: 2275155. DOI: 10.1093/nar/gkm1179. View

14.

Hochstrasser M, Ellison M, Chau V, Varshavsky A . The short-lived MAT alpha 2 transcriptional regulator is ubiquitinated in vivo. Proc Natl Acad Sci U S A. 1991; 88(11):4606-10. PMC: 51714. DOI: 10.1073/pnas.88.11.4606. View

15.

Musters W, Venema J, Van der Linden G, Van Heerikhuizen H, Klootwijk J, Planta R . A system for the analysis of yeast ribosomal DNA mutations. Mol Cell Biol. 1989; 9(2):551-9. PMC: 362631. DOI: 10.1128/mcb.9.2.551-559.1989. View

16.

Kadaba S, Krueger A, Trice T, Krecic A, Hinnebusch A, Anderson J . Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 2004; 18(11):1227-40. PMC: 420349. DOI: 10.1101/gad.1183804. View

17.

van Hoof A, Frischmeyer P, Dietz H, Parker R . Exosome-mediated recognition and degradation of mRNAs lacking a termination codon. Science. 2002; 295(5563):2262-4. DOI: 10.1126/science.1067272. View

18.

Suter B, Fetchko M, Imhof R, Graham C, Stoffel-Studer I, Zbinden C . Examining protein protein interactions using endogenously tagged yeast arrays: the cross-and-capture system. Genome Res. 2007; 17(12):1774-82. PMC: 2099586. DOI: 10.1101/gr.6667007. View

19.

Doma M, Parker R . Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation. Nature. 2006; 440(7083):561-4. PMC: 1839849. DOI: 10.1038/nature04530. View

20.

Frischmeyer P, van Hoof A, ODonnell K, Guerrerio A, Parker R, Dietz H . An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science. 2002; 295(5563):2258-61. DOI: 10.1126/science.1067338. View