The emerging role of RNA and DNA editing in cancer

Avesson, Lotta; Barry, Guy

doi:10.1016/j.bbcan.2014.03.001

Cited by 30 publications

(32 citation statements)

References 113 publications

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“…For example, while the the APOBEC family is important in embryogenesis, the adenosine deaminase acting on RNA (ADAR) family is more important in brain development (19). Nonetheless, the current study identified no definite changes in APOBEC expression among the meningiomas in this series.…”

Section: Discussioncontrasting

confidence: 60%

“…Recent studies have indicated that normal cellular enzymatic activity may contribute to the genomic changes associated with various neoplasias (1)(2)(3). Apolipoprotein B mRNA-editing enzymes (APOBEC) comprise a family of enzymes that protect immune function and are involved in mRNA editing; their cytosine deaminase activity may also induce base substitutions in the genomes of malignancies (1,2).…”

Section: Introductionmentioning

confidence: 99%

“…Apolipoprotein B mRNA-editing enzymes (APOBEC) comprise a family of enzymes that protect immune function and are involved in mRNA editing; their cytosine deaminase activity may also induce base substitutions in the genomes of malignancies (1,2).…”

Section: Introductionmentioning

confidence: 99%

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APOBEC3B expression in human leptomeninges and meningiomas

2016

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Abstract. Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas. IntroductionRecent studies have indicated that normal cellular enzymatic activity may contribute to the genomic changes associated with various neoplasias (1-3). Apolipoprotein B mRNA-editing enzymes (APOBEC) comprise a family of enzymes that protect immune function and are involved in mRNA editing; their cytosine deaminase activity may also induce base substitutions in the genomes of malignancies (1,2).APOBEC3B is a cytosine deaminase that is responsible for the deamination of cytosines in the genome of host cells, producing cytosine to thymidine mutations (2). Recently studies have found that APOBEC3B is overexpressed in several types of malignancy, resulting in clusters of C>T mutations that are considered to be the signature of APOBEC mutation in tumors. Analysis of whole-genome and whole-exome sequencing data from various types of malignancy have implicated APOBEC members in mRNA editing and the production of cytosine mutation clusters in the development or progression of numerous neoplastic processes, encompassing lung, breast, hepatic and hematopoietic malignancies (4-9). APOBEC3B overexpression has been identified in breast, head and neck cancers (7-10). Although APOBEC3B expression has not been studied in meningiomas, the presence of C>T point mutations in some meningioma cases raises the possibility that APOBEC3B may participate in the pathogenesis of at least a subset of meningiomas (11).The present study evaluated APOBEC3B expression in addition to mutations in a series of normal leptomeninges, an...

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Section: Discussioncontrasting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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APOBEC3B expression in human leptomeninges and meningiomas

2016

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“…Moreover, recent reports have also revealed that APOBEC mediated editing is responsible for characteristic DNA mutations in multiple cancer types including bladder, cervical, breast, head and neck, and lung cancers. 2 The ADAR family is comprised of 3 members, ADAR1 (which include 2 isoforms ADAR1p150 and ADAR1p110), ADAR 2, and ADAR 3. ADARs primarily edit adenosine residues in 3 0 UTR and intronic regions of both coding and non-coding RNAs, suggesting a prominent regulatory role in mRNA translation and regulation of the RNAi pathway.…”

Section: Apobec and Adar Rna Editingmentioning

confidence: 99%

RNA editing, epitranscriptomics, and processing in cancer progression

Witkin

Hanlon

Strasburger

et al. 2014

Cancer Biology & Therapy

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The transcriptome is extensively and dynamically regulated by a network of RNA modifying factors. RNA editing enzymes APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and ADAR (adenosine deaminase, RNA-specific) irreversibly recode primary RNA sequences, whereas newly described methylases (writers) and demethylases (erasers) dynamically alter RNA molecules in response to environmental conditions. RNA modifications can affect RNA splicing, nuclear-cytoplasmic transport, translation, and regulation of gene expression by RNA interference. In addition, tRNA base modifications, processing, and regulated cleavage have been shown to alter global patterns of mRNA translation in response to cellular stress pathways. Recent studies, some of which were discussed at this workshop, have rekindled interest in the emerging roles of RNA modifications in health and disease. On September 10th, 2014, the Division of Cancer Biology, NCI sponsored a workshop to explore the role of epitranscriptomic RNA modifications and tRNA processing in cancer progression. The workshop attendees spanned a scientific range including chemists, virologists, and RNA and cancer biologists. The goal of the workshop was to explore the interrelationships between RNA editing, epitranscriptomics, and RNA processing and the enzymatic pathways that regulate these activities in cancer initiation and progression. At the conclusion of the workshop, a general discussion focused on defining the major challenges and opportunities in this field, as well as identifying the tools, technologies, resources and community efforts required to accelerate research in this emerging area.

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“…Furthermore, we and others have found that there are other types of RNA-DNA sequence differences (RDDs) that are unlikely to be mediated by these deaminases (Li et al 2011;Bahn et al 2012;Bar-Yaacov et al 2013;Rubio et al 2013;Turner et al 2015). These events are found in normal cells, and altered patterns of RDDs were found in neurologic diseases (van Leeuwen et al 1998;Silberberg et al 2012;Krestel et al 2013;Wang et al 2014) and in cancers (Klimek-Tomczak et al 2006;Martinez et al 2008;Lee et al 2013;Avesson and Barry 2014;Han et al 2014;Niavarani et al 2015). Although differences between RNA and their corresponding DNA templates were known for many years, their discoveries in human beyond the editing events mediated by ADAR and APOBEC families of deaminases were debated.…”

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confidence: 95%

RNA–DNA sequence differences in Saccharomyces cerevisiae

et al. 2016

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Alterations of RNA sequences and structures, such as those from editing and alternative splicing, result in two or more RNA transcripts from a DNA template. It was thought that in yeast, RNA editing only occurs in tRNAs. Here, we found that Saccharomyces cerevisiae have all 12 types of RNA-DNA sequence differences (RDDs) in the mRNA. We showed these sequence differences are propagated to proteins, as we identified peptides encoded by the RNA sequences in addition to those by the DNA sequences at RDD sites. RDDs are significantly enriched at regions with R-loops. A screen of yeast mutants showed that RDD formation is affected by mutations in genes regulating R-loops. Loss-of-function mutations in ribonuclease H, senataxin, and topoisomerase I that resolve RNA-DNA hybrids lead to increases in RDD frequency. Our results demonstrate that RDD is a conserved process that diversifies transcriptomes and proteomes and provide a mechanistic link between R-loops and RDDs.

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The emerging role of RNA and DNA editing in cancer

Cited by 30 publications

References 113 publications

APOBEC3B expression in human leptomeninges and meningiomas

APOBEC3B expression in human leptomeninges and meningiomas

RNA editing, epitranscriptomics, and processing in cancer progression

RNA–DNA sequence differences in Saccharomyces cerevisiae

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