Review
Cell Biology
Jizhe Liu, Fei Wang, Yindan Zhang, Jingfeng Liu, Bixing Zhao
Summary: RNA stability, RNA-protein interaction, and correct protein translation are significant forces in driving the transition from normal cell to malignant tumor. ADAR1 is an RNA editing enzyme that modifies the transcriptome by catalyzing the deamination of adenosine to inosine. Dysregulation of ADAR1 can lead to aberrant editing and affect phenotypic changes in cancer. ADAR1's overediting phenomenon is observed in many cancers and promotes tumor progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Omer An, Yangyang Song, Xinyu Ke, Jimmy Bok-Yan So, Raghav Sundar, Henry Yang, Sun Young Rha, Ming Hui Lee, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Matthew Chau Hsien Ng, Erwin Tantoso, Leilei Chen, Patrick Tan, Wei Peng Yong
Summary: This study introduces a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, offering a new tool for improved patient stratification and response to therapy.
Article
Chemistry, Multidisciplinary
Steve D. Knutson, Robert A. Arthur, H. Richard Johnston, Jennifer M. Heemstra
Summary: The study presents an EndoV-linked immunosorbency assay (EndoVLISA) for rapid measurement of global A-to-I editing signatures in cellular RNA. The method is cost-effective, straightforward, and suitable for disease detection and drug development applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Meng How Tan
Summary: Adenosine-to-inosine (A-to-I) RNA editing is a gene regulatory mechanism that is widespread in many metazoans and plays a key role in diverse biological processes. The ADAR family of enzymes, including ADAR1, ADAR2, and ADAR3, catalyzes this editing process. A-to-I editing can generate new protein isoforms and influence RNA processing pathways. ADAR1 is especially important in preventing aberrant activation of the innate immune system. However, the identification of A-to-I editing sites remains challenging, and nanopore sequencing technology shows promise in addressing this issue.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Oncology
Phaik Ju Teoh, Mun Yee Koh, Wee Joo Chng
Summary: Adenosine-to-inosine (A-to-I) editing is the most prevalent type of RNA editing in humans, and aberrant ADAR-mediated-editing is a prominent feature in a variety of cancers. The functions of ADARs in hematological malignancies have been recently revealed, opening up possibilities for novel therapeutic approaches.
Article
Multidisciplinary Sciences
Knud Larsen, Mads Peter Heide-Jorgensen
Summary: RNA editing is a post-transcriptional process that can lead to proteomic sequence variation. The most common type is A-to-I editing, mediated by ADAR enzymes. Studies have shown conservation of A-to-I editing in selected mRNAs between pigs, bowhead whales, humans, and two shark species, with some novel editing sites identified.
Article
Cardiac & Cardiovascular Systems
Karoline E. Kokot, Jasmin M. Kneuer, David John, Sabine Rebs, Maximilian N. Moebius-Winkler, Stephan Erbe, Marion Mueller, Michael Andritschke, Susanne Gaul, Bilal N. Sheikh, Jan Haas, Holger Thiele, Oliver J. Mueller, Susanne Hille, Florian Leuschner, Stefanie Dimmeler, Katrin Streckfuss-Boemeke, Benjamin Meder, Ulrich Laufs, Jes-Niels Boeckel
Summary: Alterations of RNA editing, especially A-to-I RNA editing, contribute to human diseases, including heart failure. This study demonstrates that reduced RNA editing, primarily caused by Alu elements, is associated with increased circRNA levels and impaired sarcomere regularity in failing human hearts. ADAR2, a key enzyme involved in A-to-I RNA editing, is decreased in failing hearts, leading to elevated circRNA levels. The reduced ADAR2 activity also represses the formation of double-stranded RNA structures and promotes linear mRNA splicing. These findings provide important insights into the role of RNA editing and circRNA formation in human diseases, particularly heart failure.
BASIC RESEARCH IN CARDIOLOGY
(2022)
Article
Medicine, Research & Experimental
Li Jiang, Yajing Hao, Changwei Shao, Qiulian Wu, Briana C. Prager, Ryan C. Gimple, Gabriele Sulli, Leo J. Y. Kim, Guoxin Zhang, Zhixin Qiu, Zhe Zhu, Xiang-Dong Fu, Jeremy N. Rich
Summary: This study reveals the role of A-to-I RNA editing mediated by ADAR1 in GBM stem cells and its potential as a therapeutic strategy. The elevated expression of ADAR1 and global RNA editomes in GSCs suggest their involvement in therapeutic resistance and relapse. Inhibition of ADAR1 or the upstream JAK/STAT pathway impairs GSC self-renewal and stemness. Additionally, the study highlights the critical role of RNA editing in ganglioside catabolism and its impact on GSCs.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Shuqian Zhang, Bo Yuan, Jixin Cao, Liting Song, Jinlong Chen, Jiayi Qiu, Zilong Qiu, Xing-Ming Zhao, Jingqi Chen, Tian-Lin Cheng
Summary: The study demonstrates that 25 engineered TadA orthologs can generate functional ABEs, CBEs, or ACBEs with minimized off-target effects through single/double mutations. It is found that cytidine and adenosine deaminases are required for cytosine and adenine editing, respectively, and no single deaminase can enable concurrent editing of both bases. Additionally, distinct properties of cytidine and adenosine deaminases lead to different types of off-target effects.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Guo-Liang Zheng, Guo-Jun Zhang, Yan Zhao, Zhi-Chao Zheng
Summary: An abnormality in the regulation of ADAR enzymes was closely associated with aggressive behavior and poor prognosis in colorectal carcinoma. This study investigated the relationship among transcript factors-microRNAs regulatory network, immune environment, and ADAR gene in CRC. The findings suggested that ADAR could be a novel immune treatment target in CRC.
JOURNAL OF ONCOLOGY
(2023)
Article
Medicine, General & Internal
Yin-Chao Tang, Chang-Shun Yang, Ming-Xing Liang, Yong Zhang, Yuan Liu, Shao-Hui Zou, Shu-Fan Shi
Summary: We analyzed the editing data and clinical data of 251 bladder cancer patients and identified prognosis-associated ATIRE loci. A prediction model for overall survival of bladder cancer patients was constructed. Patients with high ATIRE scores had worse prognosis, and their host gene expression and immune cell infiltration showed significant changes. This study provides new prognostic markers for bladder cancer research.
Article
Biochemistry & Molecular Biology
Turnee N. Malik, Erin E. Doherty, Vandana M. Gaded, Theodore M. Hill, Peter A. Beal, Ronald B. Emeson
Summary: ADAR-mediated RNA editing modulates various cellular pathways such as innate immunity and protein recoding and is considered as a strategy for treating genetic disorders. Research has shown that intracellular acidification increases RNA editing, mainly due to enhanced ADAR base-flipping and deamination rate under acidic pH conditions.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Mikhail A. Moldovan, Zoe S. Chervontseva, Daria S. Nogina, Mikhail S. Gelfand
Summary: RNA editing is a common phenomenon, particularly in soft-bodied cephalopods, where thousands of editing sites have been identified. These editing sites tend to cluster and contribute significantly to transcriptome diversity. Different types of editing site clusters have been identified, and their formation may be influenced by RNA structural features and mechanisms.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Jiarui Li, Tomoko Oonishi, Guangyao Fan, Matomo Sakari, Toshifumi Tsukahara
Summary: This study presents a strategy to enhance the editing efficiency of site-directed RNA editing (SDRE) system by redirecting exogenous ADARs to specific sites using antisense RNA oligonucleotides.
APPLIED SCIENCES-BASEL
(2023)
Article
Chemistry, Multidisciplinary
Xue-Jiao You, Lin Li, Tong-Tong Ji, Neng-Bin Xie, Bi-Feng Yuan, Yu-Qi Feng
Summary: 6-Thioguanine (6TG) is a widely used chemotherapeutic agent for the treatment of human diseases. It can be metabolically converted into nucleotides that are incorporated into the genome and induce cell death. This study investigated the effect of 6TG on RNA modifications and found that it elevated A-to-I editing and decreased cell viability. This study reveals a new mechanism of the cytotoxicity of 6TG.
CHINESE CHEMICAL LETTERS
(2023)
Letter
Cardiac & Cardiovascular Systems
Joseph B. Moore, Ghazal Sadri, Annalara G. Fischer, Tyler Weirick, Giuseppe Militello, Marcin Wysoczynski, Anna M. Gumpert, Thomas Braun, Shizuka Uchida
CIRCULATION RESEARCH
(2020)
Article
Critical Care Medicine
Christoph M. Zehendner, Chanil Valasarajan, Astrid Werner, Jes-Niels Boeckel, Florian C. Bischoff, David John, Tyler Weirick, Simone F. Glaser, Oliver Rossbach, Nicolas Jae, Shemsi Demolli, Fatemeh Khassafi, Ke Yuan, Vinicio A. de Jesus Perez, Katharina M. Michalik, Wei Chen, Werner Seeger, Andreas Guenther, Roxana M. Wasnick, Shizuka Uchida, Andreas M. Zeiher, Stefanie Dimmeler, Soni S. Pullamsetti
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2020)
Article
Cardiac & Cardiovascular Systems
Prabhash Kumar Jha, Aatira Vijay, Arda Halu, Shizuka Uchida, Masanori Aikawa
Summary: SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, belonging to the coronavirus family along with MERS-CoV and SARS-CoV. A study analyzed gene expression datasets to identify unique transcriptional signatures of human lung cells infected with SARS-CoV-2 compared to MERS-CoV or SARS-CoV, finding potential differences in the immune response and cellular function that may contribute to the severity of COVID-19.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Timothy N. Audam, Caitlin M. Howard, Lauren F. Garrett, Yi Wei Zheng, James A. Bradley, Kenneth R. Brittian, Matthew W. Frank, Kyle L. Fulghum, Miklos Polos, Szilvia Herczeg, Bela Merkely, Tamas Radovits, Shizuka Uchida, Bradford G. Hill, Sujith Dassanayaka, Suzanne Jackowski, Steven P. Jones
Summary: This study shows that limiting cardiac CoA levels via PANK deletion exacerbated ventricular remodeling during pressure overload. The metabolic alterations associated with Pank1 deletion may underlie the exacerbated cardiac phenotype during pressure overload.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Steven P. Jones
CIRCULATION RESEARCH
(2021)
Editorial Material
Peripheral Vascular Disease
Pilar Alcaide, Steven P. Jones
Review
Pharmacology & Pharmacy
Amit Kumar Rai, Brooke Lee, Carleigh Hebbard, Shizuka Uchida, Venkata Naga Srikanth Garikipati
Summary: Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs found widely in the human heart, with emerging evidence suggesting they play regulatory roles in various cardiovascular diseases. Current understanding of circRNA focuses on their classification, biogenesis, function, stability, degradation mechanisms, and their potential as promising targets for understanding and treating CVD.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Mohammed Rabiul Hosen, Qian Li, Yangyang Liu, Andreas Zietzer, Katharina Maus, Philip Goody, Shizuka Uchida, Eicke Latz, Nikos Werner, Georg Nickenig, Felix Jansen
Summary: Certain long noncoding RNAs (lncRNAs) are dysregulated in circulating extracellular vesicles of patients with coronary artery disease (CAD). Two lncRNAs, PUNISHER and GAS5, are significantly increased in CAD patients. The intercellular transfer of EV-incorporated PUNISHER promotes a pro-angiogenic phenotype through a VEGFA-dependent mechanism.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Cardiac & Cardiovascular Systems
Merry L. Lindsey, Keith R. Brunt, Jonathan A. Kirk, Petra Kleinbongard, John W. Calvert, Lisandra E. de Castro Bras, Kristine Y. DeLeon-Pennell, Dominic P. Del Re, Nikolaos G. Frangogiannis, Stefan Frantz, Richard J. Gumina, Ganesh V. Halade, Steven P. Jones, Rebecca H. Ritchie, Francis G. Spinale, Edward B. Thorp, Crystal M. Ripplinger, Zamaneh Kassiri
Summary: This study evaluated different methods for inducing myocardial infarction in mouse models, identified opportunities for consolidating methods, and recognized that reperfused and nonreperfused myocardial infarctions yield different responses. The overall goal of compiling this consensus statement is to unify best practices regarding mouse myocardial infarction models to enhance interpretation and enable comparative examination across studies and laboratories. These guidelines aim to establish rigor and reproducibility, providing greater potential for clinical translation.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Toxicology
Igor N. Zelko, Sujith Dassanayaka, Marina Malovichko, Caitlin M. Howard, Lauren F. Garrett, Shizuka Uchida, Kenneth R. Brittian, Daniel J. Conklin, Steven P. Jones, Sanjay Srivastava
Summary: Benzene, a common environmental pollutant, is associated with an increased risk of heart failure and compromises cardiac function by promoting endothelial activation and neutrophil recruitment.
TOXICOLOGICAL SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Kyle L. Fulghum, Juliette B. Smith, Julia Chariker, Lauren F. Garrett, Kenneth R. Brittian, Pawel K. Lorkiewicz, Lindsey A. McNally, Shizuka Uchida, Steven P. Jones, Bradford G. Hill, Helen E. Collins
Summary: The goal of this study was to develop an atlas of the metabolic, transcriptional, and proteomic changes in the maternal heart during and after pregnancy. The results showed significant increases in heart size, cardiac hypertrophy, and myocyte cross-sectional area during pregnancy and post-birth, accompanied by changes in metabolites, gene expression, and protein levels. These findings provide important insights into the coordinated molecular changes that occur in the maternal heart during and after pregnancy.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ghazal Sadri, Annalara G. Fischer, Kenneth R. Brittian, Erin Elliott, Matthew A. Nystoriak, Shizuka Uchida, Marcin Wysoczynski, Andrew Leask, Steven P. Jones, Joseph B. Moore
Summary: Collagen XIX is primarily produced by fibroblasts and smooth muscle cells in the adult murine heart. It plays a role in regulating cardiac structure and function, potentially by modulating the organization of fibrillar collagen within the extracellular matrix.
Article
Hospitality, Leisure, Sport & Tourism
Kyle Fulghum, Helen E. Collins, Steven P. Jones, Bradford G. Hill
Summary: This study used metabolomics to analyze the metabolic changes in the hearts of mice following exercise, and found sex-dependent differences in cardiac metabolism. The female heart is more responsive to physiological stress caused by exercise.
JOURNAL OF SPORT AND HEALTH SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Venkata Naga Srikanth Garikipati, Shizuka Uchida
Summary: Most of the mammalian genome is transcribed as RNA, with majority being non-protein-coding RNAs (ncRNAs) that have diverse functions. Due to lack of sequence homologies among ncRNA species, it is challenging to infer their functions by examining sequence patterns. Increasing evidence suggests that various enzymes modify ncRNAs, leading to the emergence of a new field called epitranscriptomics.
Article
Biochemistry & Molecular Biology
Kasper Thystrup Karstensen, Aleks Schein, Andreas Petri, Martin Bogsted, Karen Dybkaer, Shizuka Uchida, Sakari Kauppinen
Summary: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, with 30%-40% of patients eventually relapsing or becoming refractory to treatment. Long non-coding RNAs (lncRNAs) play important roles in the pathogenesis and progression of DLBCL, providing molecular signatures for further research.
