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https://www.readbyqxmd.com/read/29203771/alu-dependent-rna-editing-of-gli1-promotes-malignant-regeneration-in-multiple-myeloma
#1
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
#2
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
#3
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
#4
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
#5
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...
November 10, 2017: RNA
https://www.readbyqxmd.com/read/29093448/structure-mediated-modulation-of-mrna-abundance-by-a-to-i-editing
#6
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
https://www.readbyqxmd.com/read/29061182/editing-inducer-elements-increases-a-to-i-editing-efficiency-in-the-mammalian-transcriptome
#7
Chammiran Daniel, Albin Widmark, Ditte Rigardt, Marie Öhman
BACKGROUND: Adenosine to inosine (A-to-I) RNA editing has been shown to be an essential event that plays a significant role in neuronal function, as well as innate immunity, in mammals. It requires a structure that is largely double-stranded for catalysis but little is known about what determines editing efficiency and specificity in vivo. We have previously shown that some editing sites require adjacent long stem loop structures acting as editing inducer elements (EIEs) for efficient editing...
October 23, 2017: Genome Biology
https://www.readbyqxmd.com/read/29061157/promoting-rna-editing-by-adar-attraction
#8
Miri Danan-Gotthold, Erez Y Levanon
Concentration is important and not only while driving; a new study indicates how an adjacent genomic element helps to increase the efficiency of a specific adenosine to inosine RNA editing reaction, by providing a means to increase the local concentration of the RNA editing enzyme ADAR.
October 23, 2017: Genome Biology
https://www.readbyqxmd.com/read/29022589/dynamic-landscape-and-regulation-of-rna-editing-in-mammals
#9
Meng How Tan, Qin Li, Raghuvaran Shanmugam, Robert Piskol, Jennefer Kohler, Amy N Young, Kaiwen Ivy Liu, Rui Zhang, Gokul Ramaswami, Kentaro Ariyoshi, Ankita Gupte, Liam P Keegan, Cyril X George, Avinash Ramu, Ni Huang, Elizabeth A Pollina, Dena S Leeman, Alessandra Rustighi, Y P Sharon Goh, Ajay Chawla, Giannino Del Sal, Gary Peltz, Anne Brunet, Donald F Conrad, Charles E Samuel, Mary A O'Connell, Carl R Walkley, Kazuko Nishikura, Jin Billy Li
Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering selected nucleotides in RNA molecules. Although many editing sites have recently been discovered, the extent to which most sites are edited and how the editing is regulated in different biological contexts are not fully understood. Here we report dynamic spatiotemporal patterns and new regulators of RNA editing, discovered through an extensive profiling of A-to-I RNA editing in 8,551 human samples (representing 53 body sites from 552 individuals) from the Genotype-Tissue Expression (GTEx) project and in hundreds of other primate and mouse samples...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/29017946/cloning-and-expression-of-malabar-grouper-epinephelus-malabaricus-adar1-gene-in-response-to-immune-stimulants-and-nervous-necrosis-virus
#10
Thirunavukkarasu Periyasamy, Joan Tang Xiao Joe, Ming-Wei Lu
ADARs are RNA editing catalysts that bind double-stranded RNA and convert adenosine to inosine, a process that can lead to destabilization of dsRNA structures and suppression of mRNA translation. In mammals, ADAR1 genes are involved in various cellular pathways, including interferon (IFN)-mediated response. However, the function of fish ADAR1 remains unclear. We report here the cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long, consisting of an open reading frame encoding a putative protein of 1381 amino acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28985428/an-rna-editing-dsrna-binding-independent-gene-regulatory-mechanism-of-adars-and-its-clinical-implication-in-cancer
#11
Lihua Qi, Yangyang Song, Tim Hon Man Chan, Henry Yang, Chi Ho Lin, Daryl Jin Tai Tay, HuiQi Hong, Sze Jing Tang, Kar Tong Tan, Xi Xiao Huang, Jaymie Siqi Lin, Vanessa Hui En Ng, Julien Jean Pierre Maury, Daniel G Tenen, Leilei Chen
Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3' untranslated regions (3'UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3'UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3'UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28974449/mechanisms-and-implications-of-adar-mediated-rna-editing-in-cancer
#12
Chen Wang, Jun Zou, Xiangyi Ma, Edward Wang, Guang Peng
Adenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine (A) to inosine (I) in double-stranded RNAs. Inosine exhibits similar properties as guanosine. As a result, A-to-I editing has a great impact on edited RNAs, not only affecting the base pairing properties, but also altering codons after translation. A-to-I editing are known to mediate and diversify transcripts. However, the overall biological effect of ADARs are still largely unknown. Aberrant ADAR activity and editing dysregulation are present in a variety of cancers, including hepatocellular carcinoma, chronic myelogenous leukemia, glioblastoma and melanoma...
September 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28969707/massive-a-to-i-rna-editing-is-common-across-the-metazoa-and-correlates-with-dsrna-abundance
#13
Hagit T Porath, Binyamin A Knisbacher, Eli Eisenberg, Erez Y Levanon
BACKGROUND: Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional modification catalyzed by the ADAR (adenosine deaminase that acts on RNA) enzymes, which are ubiquitously expressed among metazoans. Technical requirements have limited systematic mapping of editing sites to a small number of organisms. Thus, the extent of editing across the metazoan lineage is largely unknown. RESULTS: Here, we apply a computational procedure to search for RNA-sequencing reads containing clusters of editing sites in 21 diverse organisms...
October 2, 2017: Genome Biology
https://www.readbyqxmd.com/read/28968662/large-scale-prediction-of-adar-mediated-effective-human-a-to-i-rna-editing
#14
Li Yao, Heming Wang, Yuanyuan Song, Zhen Dai, Hao Yu, Ming Yin, Dongxu Wang, Xin Yang, Jinlin Wang, Tiedong Wang, Nan Cao, Jimin Zhu, Xizhong Shen, Guangqi Song, Yicheng Zhao
Adenosine-to-inosine (A-to-I) editing by adenosine deaminase acting on the RNA (ADAR) proteins is one of the most frequent modifications during post- and co-transcription. To facilitate the assignment of biological functions to specific editing sites, we designed an automatic online platform to annotate A-to-I RNA editing sites in pre-mRNA splicing signals, microRNAs (miRNAs) and miRNA target untranslated regions (3' UTRs) from human (Homo sapiens) high-throughput sequencing data and predict their effects based on large-scale bioinformatic analysis...
August 10, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28928239/the-rna-editing-enzyme-adar-promotes-lung-adenocarcinoma-migration-and-invasion-by-stabilizing-fak
#15
Elianna M Amin, Yuan Liu, Su Deng, Kay See Tan, Neel Chudgar, Marty W Mayo, Francisco Sanchez-Vega, Prasad S Adusumilli, Nikolaus Schultz, David R Jones
Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28925356/the-c-elegans-neural-editome-reveals-an-adar-target-mrna-required-for-proper-chemotaxis
#16
Sarah N Deffit, Brian A Yee, Aidan C Manning, Suba Rajendren, Pranathi Vadlamani, Emily C Wheeler, Alain Domissy, Michael C Washburn, Gene W Yeo, Heather A Hundley
ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28913566/adar-rna-editing-in-human-disease-more-to-it-than-meets-the-i
#17
REVIEW
Angela Gallo, Dragana Vukic, David Michalík, Mary A O'Connell, Liam P Keegan
We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi-Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction...
September 2017: Human Genetics
https://www.readbyqxmd.com/read/28874170/protein-recoding-by-adar1-mediated-rna-editing-is-not-essential-for-normal-development-and-homeostasis
#18
Jacki E Heraud-Farlow, Alistair M Chalk, Sandra E Linder, Qin Li, Scott Taylor, Joshua M White, Lokman Pang, Brian J Liddicoat, Ankita Gupte, Jin Billy Li, Carl R Walkley
BACKGROUND: Adenosine-to-inosine (A-to-I) editing of dsRNA by ADAR proteins is a pervasive epitranscriptome feature. Tens of thousands of A-to-I editing events are defined in the mouse, yet the functional impact of most is unknown. Editing causing protein recoding is the essential function of ADAR2, but an essential role for recoding by ADAR1 has not been demonstrated. ADAR1 has been proposed to have editing-dependent and editing-independent functions. The relative contribution of these in vivo has not been clearly defined...
September 5, 2017: Genome Biology
https://www.readbyqxmd.com/read/28820319/a-to-i-rna-editing-thinking-beyond-the-single-nucleotide
#19
Nabeel S Ganem, Ayelet T Lamm
Adenosine-to-inosine RNA editing is a conserved process, which is performed by ADAR enzymes. By changing nucleotides in coding regions of genes and altering codons, ADARs expand the cell's protein repertoire. This function of the ADAR enzymes is essential for human brain development. However, most of the known editing sites are in non-coding repetitive regions in the transcriptome and the purpose of editing in these regions is unclear. Recent studies, which have shown that editing levels of transcripts vary between tissues and developmental stages in many organisms, suggest that the targeted RNA and ADAR editing are both regulated...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28762759/adenosine-to-inosine-rna-editing-in-health-and-disease
#20
Aikaterini Gatsiou, Nikolaos Vlachogiannis, Federica Francesca Lunella, Marco Sachse, Konstantinos Stellos
SIGNIFICANCE: Adenosine deamination in transcriptome results in the formation of inosine, a process that is called A-to-I RNA editing. Adenosine deamination is one of the more than 140 described RNA modifications. A-to-I RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes and is essential for life. Recent Advances: Accumulating evidence supports a critical role of RNA editing in all aspects of RNA metabolism, including mRNA stability, splicing, nuclear export, and localization, as well as in recoding of proteins...
September 26, 2017: Antioxidants & Redox Signaling
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