Repression of yeast RNA polymerase III by stress leads to ubiquitylation and proteasomal degradation of its largest subunit, C160

Leśniewska, Ewa; Cieśla, Małgorzata; Boguta, Magdalena

doi:10.1016/j.bbagrm.2018.10.007

Cited by 11 publications

(15 citation statements)

References 50 publications

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“…We indeed observed downregulation of selected subunits; however, in both yeast and RAW264.7 macrophages, this again occurs later than the pre-tRNA decrease and is therefore likely to be secondary to the decreased Pol III activity. This is consistent with our previously published results showing that in yeast upon metabolic stress, the downregulation of the largest Pol III subunit, C160, is delayed in regard to Pol III activity inhibition (27). We thus concluded that neither Maf1, p53, nor the decrease in Pol III levels is primarily responsible for MPA-induced Pol III inhibition.…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, under these conditions, Pol III does not dissociate completely even during prolonged treatment. This is strikingly different from the response in yeast cells upon metabolic shift from fermentation to medium with a nonfermentable carbon source, where decreases in tRNA levels and Pol III dissociation kinetics are comparable (27). We speculated that a signaling event(s) triggered by this metabolic shift, which includes Maf1 dephosphorylation (30), actively impinges on Pol III, whereas MPA treatment results in GTP depletion and perhaps Pol III stalling due to the lack of one of the substrates.…”

Section: Discussionmentioning

confidence: 65%

“…This triggers disassembly of Pol III followed by proteosomal degradation of its largest subunit, C160 (26). Ubiquitylation and proteosomal degradation of C160 were also observed as a consequence of Pol III repression upon physiological stress, which pertains to most of the polymerase complexes that dissociate from templates (27). Surprisingly, the interactions between Pol III subunits in the complexes that were retained under stress conditions became even more tight (27).…”

Section: Resultsmentioning

confidence: 99%

“…5 were used. The data related to C160 levels were taken from the work of Leśniewska et al (27) and were obtained from the same strain, MW4415, grown and treated similarly as in panel A. The error bars were omitted for the sake of figure clarity.…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of tRNA Gene Transcription by the Immunosuppressant Mycophenolic Acid

Jurkiewicz

Leśniewska

Cieśla

et al. 2020

Molecular and Cellular Biology

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Inhibition of tRNA Gene Transcription by the Immunosuppressant Mycophenolic Acid

Jurkiewicz

Leśniewska

Cieśla

et al. 2020

Molecular and Cellular Biology

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“…Interestingly, SUMO modification led to RNAPIII ubiquitylation by the heterodimeric SUMO-targeted ubiquitin ligase (STUbL) Slx5-Slx8 55 . This ubiquitin-modification was found to induce Cdc48-dependent extraction of RNAPIII from chromatin and downregulation of RNAPIII transcription, most likely by proteasomal degradation 55,56 . Given the similarities to UV-induced regulation of RNAPII-S2P, we hypothesized that also RNAPII might be regulated by Slx5-Slx8.…”

Section: Resultsmentioning

confidence: 99%

A SUMO-dependent pathway controls elongating RNA Polymerase II upon UV-induced damage

Heckmann

Kern

Pfander

et al. 2019

Sci Rep

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RnA polymerase ii (RnApii) is the workhorse of eukaryotic transcription and produces messenger RnAs and small nuclear RnAs. Stalling of RnApii caused by transcription obstacles such as DnA damage threatens functional gene expression and is linked to transcription-coupled DnA repair. to restore transcription, persistently stalled RnApii can be disassembled and removed from chromatin. this process involves several ubiquitin ligases that have been implicated in RnApii ubiquitylation and proteasomal degradation. transcription by RnApii is heavily controlled by phosphorylation of the C-terminal domain of its largest subunit Rpb1. Here, we show that the elongating form of Rpb1, marked by S2 phosphorylation, is specifically controlled upon UV-induced DNA damage. Regulation of S2phosphorylated Rpb1 is mediated by SUMOylation, the SUMO-targeted ubiquitin ligase Slx5-Slx8, the Cdc48 segregase as well as the proteasome. Our data suggest an RNAPII control pathway with striking parallels to known disassembly mechanisms acting on defective RnA polymerase iii. DNA is the macromolecule that harbors all information required for life. In eukaryotes three nuclear RNA polymerases (RNAPI-III) are necessary to read out this information. While RNAPI transcribes ribosomal RNA (rRNA) 1 , RNAPIII mediates transcription of rRNA, transfer RNAs (tRNA) and other small RNAs 2. RNAPII is important for transcription of protein-coding genes, as well as for synthesis of non-coding RNAs 3-5. All three RNA polymerases are under control of several posttranslational modifications. However, specifically transcription by RNAPII is regulated by phosphorylation that chiefly targets Rpb1's carboxyl-terminal domain (CTD) heptapeptide repeats (consensus sequence YSPTSPS) 6 , which serve as platform for factors involved in transcription, chromatin modification, mRNA splicing and export 7,8. Phosphorylation of serine-5 (S5P) of the CTD repeats appears to be largely specific for Rpb1 molecules localized to promoters 9,10. Serine-2 phosphorylation (S2P) in contrast is a hallmark for elongating polymerases and ChIP signals using S2P-specific antibodies steadily rise downstream of transcription start sites and culminate at the 3'-ends of genes 9,11-13. Highly problematic for all RNA Polymerases are bulky DNA lesions on the coding strand as they may behave as "roadblocks" leading to persistent stalling of the progressing protein complexes. A key mechanism to remove bulky DNA adducts and to avoid cell cycle arrest and cell death is nucleotide excision repair (NER) 14,15. Yet to conduct DNA repair the machinery first needs to gain access to the lesion that is masked by a stalled polymerase and here, several possibilities exist. First, the RNA polymerase can simply be released from the DNA to allow access. This has been shown to occur for RNAPI and RNAPII, but the underlying mechanism is poorly understood 16-18. Second, RNAPII backtracking from the lesion can facilitate repair without dissociation. This is made possible by the proofreading activity of RNAPII, which al...

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Stress tolerance phenotype of industrial yeast: industrial cases, cellular changes, and improvement strategies

Qiu

Zhang

Zhou

et al. 2019

Appl Microbiol Biotechnol

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Repression of yeast RNA polymerase III by stress leads to ubiquitylation and proteasomal degradation of its largest subunit, C160

Cited by 11 publications

References 50 publications

Inhibition of tRNA Gene Transcription by the Immunosuppressant Mycophenolic Acid

Inhibition of tRNA Gene Transcription by the Immunosuppressant Mycophenolic Acid

A SUMO-dependent pathway controls elongating RNA Polymerase II upon UV-induced damage

Stress tolerance phenotype of industrial yeast: industrial cases, cellular changes, and improvement strategies

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