Deletion of the non-essential Rpb9 subunit of RNA polymerase II results in pleiotropic phenotypes in Schizosaccharomyces pombe

Bhardwaj, Vaibhav; Vishwakarma, Poonam; Lynn, Andrew M.; Sharma, Nimisha

doi:10.1016/j.bbapap.2021.140654

Cited by 3 publications

(12 citation statements)

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“…It is interesting to note that there is another distinct model that points out RNA Pol II, the subunit RPB9 of RNA Pol II to be exact, initiated the TC-NER independent of the yeast CSB homolog Rad26 (Li and Smerdon, 2002 ; Li et al, 2006 ). Loss of Rpb9 leads to genomic instability, aberrant segregation of chromosomes in mitosis in yeast and cells (Wery et al, 2004 ; Sein et al, 2018 ), and severely compromised the viability of Schizosaccharomyces pombe under genotoxic stress conditions (Bhardwaj et al, 2021 ). However, whether RPB9 induces neuronal dysfunctions via TC-NER is an open question to date.…”

Section: Rna Polymerase Mediated Transcription-coupled Dna Repairmentioning

confidence: 99%

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases

Cao

Liu

et al. 2022

Front. Cell. Neurosci.

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Most of the neurodegenerative diseases and aging are associated with reactive oxygen species (ROS) or other intracellular damaging agents that challenge the genome integrity of the neurons. As most of the mature neurons stay in G0/G1 phase, replication-uncoupled DNA repair pathways including BER, NER, SSBR, and NHEJ, are pivotal, efficient, and economic mechanisms to maintain genomic stability without reactivating cell cycle. In these progresses, polymerases are prominent, not only because they are responsible for both sensing and repairing damages, but also for their more diversified roles depending on the cell cycle phase and damage types. In this review, we summarized recent knowledge on the structural and biochemical properties of distinct polymerases, including DNA and RNA polymerases, which are known to be expressed and active in nervous system; the biological relevance of these polymerases and their interactors with neuronal degeneration would be most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair; furthermore, the vicious cycle of the trinucleotide repeat (TNR) and impaired DNA repair pathway is also discussed. Unraveling the mechanisms and contextual basis of the role of the polymerases in DNA damage response and repair will promote our understanding about how long-lived postmitotic cells cope with DNA lesions, and why disrupted DNA repair contributes to disease origin, despite the diversity of mutations in genes. This knowledge may lead to new insight into the development of targeted intervention for neurodegenerative diseases.

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Section: Rna Polymerase Mediated Transcription-coupled Dna Repairmentioning

confidence: 99%

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases

Cao

Liu

et al. 2022

Front. Cell. Neurosci.

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“…S. pombe Rpb9 displays a 59% similarity with Saccharomyces cerevisiae Rpb9 and 56% similarity with its human ortholog [9]. To determine if these orthologs could functionally substitute S. pombe Rpb9, and rescue the stationary phase survival defect of S. pombe rpb9 null F I G U R E 3 rpb9 Null mutant exhibits enhanced sensitivity to oxidative stress and increased ROS accumulation during the stationary phase.…”

Section: Saccharomyces Cerevisiae and Human Rpb9 Orthologs Enhance Th...mentioning

confidence: 99%

“…Although budding yeast has been used as a model system for most of these studies, fission yeast provides a complementary model organism that diverged from budding yeast about 350 million years ago, and is also considered to be more closer to higher eukaryotes [49,50]. Interestingly, fission yeast RNA pol II contains only one subunit, Rpb9, whose absence does not lead to lethality under optimum growth conditions [8,9]. Towards understanding the physiological role(s) of Rpb9 in fission yeast, in the present study, we decided to investigate its role in survival during the stationary phase of growth, which is considered to be an indicator of the "chronological life span" [20,21] and is used to model aging of postmitotic cells as well as organismal aging F I G U R E 5 Saccharomyces cerevisiae and human Rpb9 orthologs enhance the chronological life span of fission yeast rpb9 null mutant.…”

Section: Saccharomyces Cerevisiae and Human Rpb9 Orthologs Enhance Th...mentioning

confidence: 99%

“…Orthologs of the Rpb9 subunit have also been identified in other organisms including archaebacteria, Drosophila and Trypanosoma, and it exhibits a high degree of sequence and structural conservation among all its orthologs [12][13][14]. Three distinct domains have been identified in fission yeast Rpb9, that is, an amino-terminal zinc finger domain, a central linker region, and a carboxylterminal zinc finger domain [9]. Most of the functional studies on the Rpb9 subunit have focussed on elucidating its roles in the budding yeast.…”

Section: Introductionmentioning

confidence: 99%

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Absence of the Rpb9 subunit of RNA polymerase II reduces the chronological life span in fission yeast

Bhardwaj

Sharma

2022

J Basic Microbiol

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Fission yeast RNA polymerase II consists of 12 subunits, Rpb1-Rpb12. Among these subunits, Rpb9 is the only subunit whose absence does not cause lethality under optimum growth conditions in fission yeast. However, an rpb9 null fission yeast mutant exhibits a slow-growth phenotype under optimum growth conditions and a defect in survival under environmental and genotoxic stress conditions. To further

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“…As Pol II is the most direct functional homolog of the archaeal Pol for general transcription [ 1 ], it is interesting that its TFS homolog Rpb9 is inactive for RNA cleavage, and Pol II instead employs TFIIS for cleavage activity ( Figure 1 ) [ 28 ]. This may help optimize flexibility for factors that exchange on and off Pol II, as well as elongation control/regulation independent of TFIIS [see introduction in 36 ]. This would be consistent with the idea that Pols I and III are specialized for small subsets of genes with many fewer associated factors and one integral Rpb9 homolog whose CTD is readily active for cleavage when mobilized from a storage position in which it doesn’t interfere with elongation, into the funnel-pore as needed.…”

Section: Introductionmentioning

confidence: 99%

Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III

Mishra

Maraia

2022

Journal of Cellular Immunology

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Nuclear RNA polymerase (Pol) III synthesizes large amounts of tRNAs and other short non-coding (nc)RNAs by a unique process that involves a termination-associated reinitiation-recycling mechanism. In addition to its two largest of 17 subunits, which contribute to active center RNA-DNA binding and catalytic site, a smaller subunit of ~110 aa (yeast C11, human RPC10) monitors this site, can modify its activity, and is essential for reinitiation-recycling. Distinct, but relevant to human immunity is cytoplasmic (cyto-)Pol III that is a direct sensor of AT-rich viral DNA from which it synthesizes 5’-ppp-RNA signaling molecules that activate interferon (IFN) production. Mutations in genes encoding Pol III subunits cause severe anti-viral immunodeficiency although the mechanisms responsible for cyto-Pol III initiation on this AT-rich DNA are unknown. Cyto-Pol III has also been implicated in inducing IFN in response to cytosolic mitochondrial DNA in autoimmune dysfunction. A focus of this commentary is recent biochemical and genetics research that examined the roles of the individual domains of C11 in the Pol III termination-associated reinitiation-recycling process as well as more recent cryo-EM structural and accompanying analyses, that are considered in evolutionary and other biological contexts. The N-terminal domain (NTD) of C11/RPC10 anchors at the periphery of Pol III from which a highly conserved linker extends to the mobile C-terminal RNA cleavage domain that can reach into the active center and rescue arrested complexes. Biochemical data indicate separable activities for the NTD and CTD in the transcription cycle, whereas the NTD-Linker can confer the evolutionary unique Pol III termination-reinitiation-recycling activity. A model produced from single particle cryo-EM conformations indicates that the C11-Linker-CTD swings in and out of the active center coordinated with allosteric movements of the DNA-binding clamp by the largest subunit, coupling termination to reinitiation-recycling. These may be relevant to DNA loading by cyto-Pol III during immune signaling.

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Deletion of the non-essential Rpb9 subunit of RNA polymerase II results in pleiotropic phenotypes in Schizosaccharomyces pombe

Cited by 3 publications

References 44 publications

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases

Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases

Absence of the Rpb9 subunit of RNA polymerase II reduces the chronological life span in fission yeast

Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III

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