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https://www.readbyqxmd.com/read/29617672/increased-rna-editing-may-provide-a-source-for-autoantigens-in-systemic-lupus-erythematosus
#1
Shalom Hillel Roth, Miri Danan-Gotthold, Meirav Ben-Izhak, Gideon Rechavi, Cyrille J Cohen, Yoram Louzoun, Erez Y Levanon
RNA-editing mechanisms, which induce nucleotide substitution in the RNA, increase transcript and protein diversities. Editing dysregulation has been shown to lead to grave outcomes, and transcriptome-wide aberrant RNA editing has been found in tumors. However, little is known about the involvement of editing in other diseases. Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by a loss of tolerance for autoantigens from various tissues and the production of multiple autoantibodies...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29567676/cancer-associated-rs6983267-snp-and-its-accompanying-long-noncoding-rna-ccat2-induce-myeloid-malignancies-via-unique-snp-specific-rna-mutations
#2
Maitri Y Shah, Manuela Ferracin, Valentina Pileczki, Baoqing Chen, Roxana Redis, Linda Fabris, Xinna Zhang, Cristina Ivan, Masayoshi Shimizu, Cristian Rodriguez-Aguayo, Mihnea Dragomir, Katrien Van Roosbroeck, Maria Ines Almeida, Maria Ciccone, Daniela Nedelcu, Maria Angelica Cortez, Taghi Manshouri, Steliana Calin, Muharrem Muftuoglu, Pinaki P Banerjee, Mustafa H Badiwi, Jan Parker-Thornburg, Asha Multani, James William Welsh, Marcos Roberto Estecio, Hui Ling, Ciprian Tomuleasa, Delia Dima, Hui Yang, Hector Alvarez, M James You, Milan Radovich, Elizabeth Shpall, Muller Fabbri, Katy Rezvani, Leonard Girnita, Ioana Berindan-Neagoe, Anirban Maitra, Srdan Verstovsek, Riccardo Fodde, Carlos Bueso-Ramos, Mihai Gagea, Guillermo Garcia Manero, George A Calin
The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients...
March 22, 2018: Genome Research
https://www.readbyqxmd.com/read/29491134/a-radar-defense-against-rnai
#3
REVIEW
Amy E Pasquinelli
Adenosine deaminases that act on RNA (ADARs) convert adenosines (A) to inosines (I) in stretches of dsRNA. The biological purpose of these editing events for the vast majority of ADAR substrates is largely unknown. In this issue of Genes & Development, Reich and colleagues (pp. 271-282) demonstrate that in Caenorhabditis elegans , A-to-I editing in double-stranded regions of protein-coding transcripts protects these RNAs from targeting by the RNAi pathway. Disruption of this safeguard through loss of ADAR activity coupled with enhanced RNAi results in developmental abnormalities and profound changes in gene expression that suggest aberrant induction of an antiviral response...
February 1, 2018: Genes & Development
https://www.readbyqxmd.com/read/29483152/-c-elegans-adars-antagonize-silencing-of-cellular-dsrnas-by-the-antiviral-rnai-pathway
#4
Daniel P Reich, Katarzyna M Tyc, Brenda L Bass
Cellular dsRNAs are edited by adenosine deaminases that act on RNA (ADARs). While editing can alter mRNA-coding potential, most editing occurs in noncoding sequences, the function of which is poorly understood. Using dsRNA immunoprecipitation (dsRIP) and RNA sequencing (RNA-seq), we identified 1523 regions of clustered A-to-I editing, termed editing-enriched regions (EERs), in four stages of Caenorhabditis elegans development, often with highest expression in embryos. Analyses of small RNA-seq data revealed 22- to 23-nucleotide (nt) siRNAs, reminiscent of viral siRNAs, that mapped to EERs and were abundant in adr-1;adr-2 mutant animals...
February 26, 2018: Genes & Development
https://www.readbyqxmd.com/read/29470549/genome-wide-identification-and-analysis-of-a-to-i-rna-editing-events-in-bovine-by-transcriptome-sequencing
#5
Mohammad Reza Bakhtiarizadeh, Abdolreza Salehi, Rocío Melissa Rivera
RNA editing increases the diversity of the transcriptome and proteome. Adenosine-to-inosine (A-to-I) editing is the predominant type of RNA editing in mammals and it is catalyzed by the adenosine deaminases acting on RNA (ADARs) family. Here, we used a largescale computational analysis of transcriptomic data from brain, heart, colon, lung, spleen, kidney, testes, skeletal muscle and liver, from three adult animals in order to identify RNA editing sites in bovine. We developed a computational pipeline and used a rigorous strategy to identify novel editing sites from RNA-Seq data in the absence of corresponding DNA sequence information...
2018: PloS One
https://www.readbyqxmd.com/read/29457714/selective-recognition-of-rna-substrates-by-adar-deaminase-domains
#6
Yuru Wang, SeHee Park, Peter A Beal
Adenosine deamination is one of the most prevalent post-transcriptional modifications in mRNA and is catalyzed by ADAR1 and ADAR2 in humans. ADAR1 and ADAR2 have different substrate selectivity, which is believed to mainly originate from the proteins' deaminase domains (hADAR1d and hADAR2d, respectively). RNA-seq of the S. cerevisiae transcriptome subjected to ADAR-catalyzed RNA editing identified substrates with common secondary structure features preferentially edited by hADAR1d over hADAR2d. The relatively small size and efficient reaction of one of these substrates suggested it could be useful for further study of the hADAR1d reaction...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29419780/differential-enzymatic-activity-of-rat-adar2-splicing-variants-is-due-to-altered-capability-to-interact-with-rna-in-the-deaminase-domain
#7
Alice Filippini, Daniela Bonini, Edoardo Giacopuzzi, Luca La Via, Fabrizio Gangemi, Marina Colombi, Alessandro Barbon
In mammals, adenosine (A) to inosine (I) RNA editing is performed by adenosine deaminases acting on RNA (ADAR), ADAR1 and ADAR2 enzymes, encoded by mRNAs that might undergo splicing process. In rat, two splicing events produce several isoforms of ADAR2, called ADAR2a, ADAR2b, ADAR2e, and ADAR2f, but only ADAR2a and ADAR2b are translated into an active protein. In particular, they differ for ten amino acids located in the catalytic domain of ADAR2b. Here, we focused on these two isoforms, analyzing the splicing pattern and their different function during rat neuronal maturation...
February 8, 2018: Genes
https://www.readbyqxmd.com/read/29396793/post-transcriptional-regulation-of-line-1-retrotransposition-by-aid-apobec-and-adar-deaminases
#8
REVIEW
Elisa Orecchini, Loredana Frassinelli, Silvia Galardi, Silvia Anna Ciafrè, Alessandro Michienzi
Long interspersed element-1 (LINE-1 or L1) retrotransposons represent the only functional family of autonomous transposable elements in humans and formed 17% of our genome. Even though most of the human L1 sequences are inactive, a limited number of copies per individual retain the ability to mobilize by a process termed retrotransposition. The ongoing L1 retrotransposition may result in insertional mutagenesis that could lead to negative consequences such as genetic disease and cancer. For this reason, cells have evolved several mechanisms of defense to restrict L1 activity...
February 2, 2018: Chromosome Research
https://www.readbyqxmd.com/read/29363430/a-comprehensive-study-on-cellular-rna-editing-activity-in-response-to-infections-with-different-subtypes-of-influenza-a-viruses
#9
Yingying Cao, Ruiyuan Cao, Yaowei Huang, Hongxia Zhou, Yuanhua Liu, Xuan Li, Wu Zhong, Pei Hao
BACKGROUND: RNA editing is an important mechanism that expands the diversity and complexity of genetic codes. The conversions of adenosine (A) to inosine (I) and cytosine (C) to uridine (U) are two prominent types of RNA editing in animals. The roles of RNA editing events have been implicated in important biological pathways. Cellular RNA editing activity in response to influenza A virus infection has not been fully characterized in human and avian hosts. This study was designed as a big data analysis to investigate the role and response of RNA editing in epithelial cells during the course of infection with various subtypes of influenza A viruses...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29363428/a-survey-on-cellular-rna-editing-activity-in-response-to-candida-albicans-infections
#10
Yaowei Huang, Yingying Cao, Jiarui Li, Yuanhua Liu, Wu Zhong, Xuan Li, Chen Chen, Pei Hao
BACKGROUND: Adenosine-to-Inosine (A-to-I) RNA editing is catalyzed by the adenosine deaminase acting on RNA (ADAR) family of enzymes, which induces alterations in mRNA sequence. It has been shown that A-to-I RNA editing events are of significance in the cell's innate immunity and cellular response to viral infections. However, whether RNA editing plays a role in cellular response to microorganism/fungi infection has not been determined. Candida albicans, one of the most prevalent human pathogenic fungi, usually act as a commensal on skin and superficial mucosal, but has been found to cause candidiasis in immunosuppression patients...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29310578/a-to-i-rna-editing-in-the-rat-brain-is-age-dependent-region-specific-and-sensitive-to-environmental-stress-across-generations
#11
Hiba Zaidan, Gokul Ramaswami, Yaela N Golumbic, Noa Sher, Assaf Malik, Michal Barak, Dalia Galiani, Nava Dekel, Jin B Li, Inna Gaisler-Salomon
BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats...
January 8, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29304330/n-6-methyladenosines-modulate-a-to-i-rna-editing
#12
Jian-Feng Xiang, Qin Yang, Chu-Xiao Liu, Man Wu, Ling-Ling Chen, Li Yang
N6 -methyladenosine (m6 A) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between m6 A-positive and m6 A-negative RNA populations. Both the presence and extent of A-to-I sites in m6 A-negative RNA transcripts suggest a negative correlation between m6 A and A-to-I. Suppression of m6 A-catalyzing enzymes results in global A-to-I RNA editing changes...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29280160/when-micrornas-meet-rna-editing-in-cancer-a-nucleotide-change-can-make-a-difference
#13
REVIEW
Yumeng Wang, Han Liang
RNA editing is a major post-transcriptional mechanism that changes specific nucleotides at the RNA level. The most common RNA editing type in humans is adenosine (A) to inosine (I) editing, which is mediated by ADAR enzymes. RNA editing events can not only change amino acids in proteins, but also affect the functions of non-coding RNAs such as miRNAs. Recent studies have characterized thousands of miRNA RNA editing events across different cancer types. Importantly, individual cases of miRNA editing have been reported to play a role in cancer development...
February 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29273356/global-transcriptome-analysis-of-rna-abundance-regulation-by-adar-in-lung-adenocarcinoma
#14
Michael F Sharpnack, Bin Chen, Dvir Aran, Idit Kosti, Douglas D Sharpnack, David P Carbone, Parag Mallick, Kun Huang
Despite tremendous advances in targeted therapies against lung adenocarcinoma, the majority of patients do not benefit from personalized treatments. A deeper understanding of potential therapeutic targets is crucial to increase the survival of patients. One promising target, ADAR, is amplified in 13% of lung adenocarcinomas and in-vitro studies have demonstrated the potential of its therapeutic inhibition to inhibit tumor growth. ADAR edits millions of adenosines to inosines within the transcriptome, and while previous studies of ADAR in cancer have solely focused on protein-coding edits, >99% of edits occur in non-protein coding regions...
January 2018: EBioMedicine
https://www.readbyqxmd.com/read/29203771/alu-dependent-rna-editing-of-gli1-promotes-malignant-regeneration-in-multiple-myeloma
#15
Elisa Lazzari, Phoebe K Mondala, Nathaniel Delos Santos, Amber C Miller, Gabriel Pineda, Qingfei Jiang, Heather Leu, Shawn A Ali, Anusha-Preethi Ganesan, Christina N Wu, Caitlin Costello, Mark Minden, Raffaella Chiaramonte, A Keith Stewart, Leslie A Crews, Catriona H M Jamieson
Despite novel therapies, relapse of multiple myeloma (MM) is virtually inevitable. Amplification of chromosome 1q, which harbors the inflammation-responsive RNA editase adenosine deaminase acting on RNA (ADAR)1 gene, occurs in 30-50% of MM patients and portends a poor prognosis. Since adenosine-to-inosine RNA editing has recently emerged as a driver of cancer progression, genomic amplification combined with inflammatory cytokine activation of ADAR1 could stimulate MM progression and therapeutic resistance. Here, we report that high ADAR1 RNA expression correlates with reduced patient survival rates in the MMRF CoMMpass data set...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146145/adars-and-editing-the-role-of-a-to-i-rna-modification-in-cancer-progression
#16
REVIEW
Kajsa Fritzell, Li-Di Xu, Jens Lagergren, Marie Öhman
Cancer arises when pathways that control cell functions such as proliferation and migration are dysregulated to such an extent that cells start to divide uncontrollably and eventually spread throughout the body, ultimately endangering the survival of an affected individual. It is well established that somatic mutations are important in cancer initiation and progression as well as in creation of tumor diversity. Now also modifications of the transcriptome are emerging as a significant force during the transition from normal cell to malignant tumor...
November 16, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29145975/in-cancer-a-to-i-rna-editing-can-be-the-driver-the-passenger-or-the-mechanic
#17
Nabeel S Ganem, Noa Ben-Asher, Ayelet T Lamm
In recent years, A-to-I RNA modifications performed by the Adenosine Deaminase Acting on RNA (ADAR) protein family were found to be expressed at altered levels in multiple human malignancies. A-to-I RNA editing changes adenosine to inosine on double stranded RNA, thereby changing transcript sequence and structure. Although A-to-I RNA editing have the potential to change essential mRNA transcripts, affecting their corresponding protein structures, most of the human editing sites identified to date reside in non-coding repetitive transcripts such as Alu elements...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29127844/the-role-of-a-to-i-rna-editing-in-cancer-development
#18
REVIEW
Xiaoyan Xu, Yumeng Wang, Han Liang
Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans, which is catalyzed in ADAR enzymes. Recent genomic studies have revealed thousands of altered RNA editing events in various cancer tissues, leading to diverse functional consequences. A critical role of individual A-to-I RNA editing events in cancer has been reported. Here, we review the current state of our knowledge on key A-to-I RNA editing events in coding and non-coding regions for their roles in cancer development and discuss their potential clinical utility...
November 8, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29127211/mechanistic-implications-of-enhanced-editing-by-a-hypertribe-rna-binding-protein
#19
Weijin Xu, Reazur Rahman, Michael Rosbash
We previously developed TRIBE, a method for the identification of cell-specific RNA-binding protein targets. TRIBE expresses an RBP of interest fused to the catalytic domain (cd) of the RNA-editing enzyme ADAR and performs adenosine-to-inosine editing on RNA targets of the RBP. However, target identification is limited by the low editing efficiency of the ADARcd. Here we describe HyperTRIBE, which carries a previously characterized hyperactive mutation (E488Q) of the ADARcd. HyperTRIBE identifies dramatically more editing sites, many of which are also edited by TRIBE but at a much lower editing frequency...
February 2018: RNA
https://www.readbyqxmd.com/read/29093448/structure-mediated-modulation-of-mrna-abundance-by-a-to-i-editing
#20
Anneke Brümmer, Yun Yang, Tracey W Chan, Xinshu Xiao
RNA editing introduces single nucleotide changes to RNA, thus potentially diversifying gene expression. Recent studies have reported significant changes in RNA editing profiles in disease and development. The functional consequences of these widespread alterations remain elusive because of the unknown function of most RNA editing sites. Here, we carry out a comprehensive analysis of A-to-I editomes in human populations. Surprisingly, we observe highly similar editing profiles across populations despite striking differences in the expression levels of ADAR genes...
November 2, 2017: Nature Communications
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