Connections between 3′ end processing and DNA damage response: Ten years later

Murphy, Michael R.; Kleiman, Frida E.

doi:10.1002/wrna.1571

Cited by 15 publications

(8 citation statements)

References 314 publications

(476 reference statements)

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“…RBMX, FUS, SF3B4, p54nrb/NONO, SFPQ, EWS and DHX36 were also over-expressed in HLNRA groups. This is suggestive of an intricate functional link between DNA damage response and RNA metabolism during low dose exposures, in line with other recent findings 30 .…”

Section: Resultssupporting

confidence: 92%

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Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC–MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifications and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein–protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro-survival cellular processes against radiation stress. PPI networks also identified an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifier PXD022380].

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Section: Resultssupporting

confidence: 92%

“…All three HLNRA groups showed marked enrichment (P ≤ 0.05, Fisher's exact test) of biological processes related to RNA processing and splicing. There was a dif- 30 .…”

Section: Quantitative Proteomics Using Itraq Based Lc-ms/msmentioning

confidence: 99%

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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“…This is in agreement with previous studies demonstrating that a common cellular response to genotoxic agents is to downregulate overall transcription, while ensuring that a subset of transcripts is modulated to mediate a targeted DNA damage response (DDR) e.g., via altered transcriptional rate, splicing and 3 0 -processing. 51,52 Within microRNA biogenesis signalling, several components of the nuclear pore complex (Nup35, 37, 62, 98, 153, 160 and 188, Ahctf1 and Pom121) were uniquely upregulated after BLM PCI , suggesting increased nucleocytoplasmic shuttling. This is in accordance with increased spliceosomal cycle, in which snRNAs are exported to the cytoplasm prior to assembly of snRNPs and re-entry into the nucleus.…”

Section: Blm Pci Mediates Enhanced Transcriptional Repression and Dna...mentioning

confidence: 99%

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Gederaas,

Sharma,

Mbarak

et al. 2023

Mol. Omics

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“…In eukaryotic cells, the untranslational region (UTR), particularly of the length of the 3′‐end poly(A) tail, contributes to the stability and translation efficiency of most mRNAs (Dreyfus & Regnier, 2002; Garneau, Wilusz, & Wilusz, 2007). The impact of mRNA 3′‐end processing on DDR has been nicely reviewed by Kleiman and her colleges (Cevher & Kleiman, 2010; Murphy & Kleiman, 2020).…”

Section: Introductionmentioning

confidence: 99%

Diverse functions of deadenylases in DNA damage response and genomic integrity

Yan

2020

WIREs RNA

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DNA damage response (DDR) is a coordinated network of diverse cellular processes including the detection, signaling, and repair of DNA lesions, the adjustment of metabolic network and cell fate determination. To deal with the unavoidable DNA damage caused by either endogenous or exogenous stresses, the cells need to reshape the gene expression profile to allow efficient transcription and translation of DDR‐responsive messenger RNAs (mRNAs) and to repress the nonessential mRNAs. A predominant method to adjust RNA fate is achieved by modulating the 3′‐end oligo(A) or poly(A) length via the opposing actions of polyadenylation and deadenylation. Poly(A)‐specific ribonuclease (PARN) and the carbon catabolite repressor 4 (CCR4)‐Not complex, the major executors of deadenylation, are indispensable to DDR and genomic integrity in eukaryotic cells. PARN modulates cell cycle progression by regulating the stabilities of mRNAs and microRNA (miRNAs) involved in the p53 pathway and contributes to genomic stability by affecting the biogenesis of noncoding RNAs including miRNAs and telomeric RNA. The CCR4‐Not complex is involved in diverse pathways of DDR including transcriptional regulation, signaling pathways, mRNA stabilities, translation regulation, and protein degradation. The RNA targets of deadenylases are tuned by the DDR signaling pathways, while in turn the deadenylases can regulate the levels of DNA damage‐responsive proteins. The mutual feedback between deadenylases and the DDR signaling pathways allows the cells to precisely control DDR by dynamically adjusting the levels of sensors and effectors of the DDR signaling pathways. Here, the diverse functions of deadenylases in DDR are summarized and the underlying mechanisms are proposed according to recent findings. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms

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Connections between 3′ end processing and DNA damage response: Ten years later

Cited by 15 publications

References 314 publications

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Proteomic analysis reveals mechanisms underlying increased efficacy of bleomycin by photochemical internalization in bladder cancer cells

Diverse functions of deadenylases in DNA damage response and genomic integrity

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