The RNA exosome affects iron response and sensitivity to oxidative stress

Tsanova, Borislava; Spatrick, Phyllis; Jacobson, Andrew D.; Hoof, Ambro van

doi:10.1261/rna.043257.113

Cited by 9 publications

(8 citation statements)

References 52 publications

(67 reference statements)

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“…Furthermore, the nuclear exosome has been demonstrated to control a number of cellular responses and processes. These include the cellular iron response and sensitivity to oxidative stress ( 73 ), silencing of heterochromatic ( 74 ) and meiotic ( 75 ) genes, as well as regulation of cellular levels of mRNAs carrying decay-promoting introns ( 76 ). To our knowledge, the evidence presented here possibly provides the first example of selective and kinetic mRNA degradation as a central paradigm, which controls intracellular mRNA targeting and thereby regulates the activity of a signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae

Sarkar

Paira

Das

2017

Nucleic Acids Research

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Unfolded protein response (UPR) is triggered by the accumulation of unfolded proteins in the endoplasmic reticulum (ER), which is accomplished by a dramatic induction of genes encoding ER chaperones. Activation of these genes involves their rapid transcription by Hac1p, encoded by the HAC1 precursor transcript harboring an intron and a bipartite element (3′-BE) in the 3′-UTR. ER stress facilitates intracellular targeting and recruitment of HAC1 pre-mRNA to Ire1p foci (requiring 3′-BE), leading to its non-spliceosomal splicing mediated by Ire1p/Rlg1p. A critical concentration of the pre-HAC1 harboring a functional 3′-BE element is governed by its 3′→5′ decay by the nuclear exosome/DRN. In the absence of stress, pre-HAC1 mRNA undergoes a rapid and kinetic 3′→5′ decay leading to a precursor pool, the majority of which lack the BE element. Stress, in contrast, causes a diminished decay, thus resulting in the production of a population with an increased abundance of pre-HAC1 mRNA carrying an intact BE, which facilitates its more efficient recruitment to Ire1p foci. This mechanism plays a crucial role in the timely activation of UPR and its prompt attenuation following the accomplishment of homeostasis. Thus, a kinetic mRNA decay provides a novel paradigm for mRNA targeting and regulation of gene expression.

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Section: Discussionmentioning

confidence: 99%

Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae

Sarkar

Paira

Das

2017

Nucleic Acids Research

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“…The exosome plays important roles in the regulation of a variety of molecular and physiological processes in different organisms, including mitotic regulation, growth, oxidative stress responses and carcinoma progression 42 43 44 45 . The aberrant activity of the exosome may cause various diseases.…”

Section: Discussionmentioning

confidence: 99%

The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

Zhang

Wan

Huang

et al. 2015

Sci Rep

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The exosome is a complex with exoribonuclease activity that regulates RNA surveillance and turnover. The exosome also plays a role in regulating the degradation of precursor mRNAs to maintain the expression of splicing variants. In Neurospora, the silencing of rrp44, which encodes the catalytic subunit of the exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and SR protein related genes. The knockdown of rrp44 also affected the assembly of the spliceosome. RNA-seq analysis revealed a global change in bulk splicing events. Exosome-mediated splicing may regulate alternative splicing of NCU05290, NCU07421 and the circadian clock gene frequency (frq). The knockdown of rrp44 led to an increased ratio of splicing variants without intron 6 (I-6) and shorter protein isoform small FRQ (s-FRQ) as a consequence. These findings suggest that the exosome controls splicing events by regulating the degradation of precursor mRNAs and the gene expression, assembly and function of the spliceosome.

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“…Thus, staining with S9.6 did not correlate with the CIN phenotype measured by the ALF assay. Given that R-loops typically lead to double strand breaks and hyperrecombination due to interference with DNA replication forks [38], which has been observed in other DIS3 mutants [36,39], we also measured the frequency of Rad52-YFP foci in the DIS3 alleles. This analysis showed no increase in Rad52 foci, further suggesting that mutant-induced DNA damage is not a likely cause of genome instability (Figure 5(c)).…”

Section: The Dis3 E729k Allele Alters Cell Cycle Progression In the Cmentioning

confidence: 99%

Exonuclease domain mutants of yeast DIS3 display genome instability

Milbury

Paul

Lari

et al. 2019

Nucleus

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The exosome functions to regulate the cellular transcriptome through RNA biogenesis, surveillance, and decay. Mutations in Dis3, a catalytic subunit of the RNA exosome with separable endonuclease and exonuclease activities, are linked to multiple myeloma. Here we report that a cancer-associated DIS3 allele, dis3 E729K , provides evidence for DIS3 functioning in mitotic fidelity in yeast. This dis3 E729K allele does not induce defects in 7S→5.8S rRNA processing, although it elicits a requirement for P-body function. While it does not significantly influence cell cycle progression alone, the allele reduces the efficiency of cell cycle arrest in strains with defects in kinetochore assembly. Finally, point mutations in the exonuclease domains of yeast Dis3 elicit genome instability phenotypes; however, these DIS3 mutations do not increase DNA damage or RNA processing defects that lead to the accumulation of polyadenylated RNA in the nucleus. These data suggest that specific DIS3 activities support mitotic fidelity in yeast.

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The RNA exosome affects iron response and sensitivity to oxidative stress

Cited by 9 publications

References 52 publications

Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae

Nuclear mRNA degradation tunes the gain of the unfolded protein response in Saccharomyces cerevisiae

The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

Exonuclease domain mutants of yeast DIS3 display genome instability

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