Article
Pharmacology & Pharmacy
Mohamed Z. Habib, Esraa M. Elnahas, Yasmin M. Aboul-Ela, Mai A. Ebeid, Marwa Tarek, Doaa R. Sadek, Eman A. Negm, Dina A. Abdelhakam, Sawsan Aboul-Fotouh
Summary: Several reports suggest that calcium permeable AMPA glutamate receptors with RNA hypo-editing at the GluA2 Q/R site and excitotoxicity-mediated neuronal death play a role in the pathogenesis of neurological disorders including autism spectrum disorder (ASD). This study examined the effects of risperidone treatment on Adar2 expression, GluA2 editing, oxidative/nitrosative stress, and neuronal death in a rat model of ASD. The results showed that risperidone improved behavioral deficits and increased Adar2 expression and GluA2 editing, while reducing oxidative/nitrosative stress and neurodegeneration.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Loredana Frassinelli, Elisa Orecchini, Sofian Al-Wardat, Marco Tripodi, Carmine Mancone, Margherita Doria, Silvia Galardi, Silvia Anna Ciafre, Alessandro Michienzi
Summary: ADAR2 acts as a suppressor of L1 retrotransposition by inhibiting its activity, forming a complex with multiple non-ribosomal ADAR2-interacting factors.
Article
Hematology
Mingrui Guo, Tim Hon Man Chan, Qiling Zhou, Omer An, Ying Li, Yangyang Song, Zi Hui Tan, Vanessa Hui En Ng, Philomina Sona Peramangalam, Zhi Qing Tan, Xinang Cao, Eisaku Iwanaga, Masao Matsuoka, Melissa G. M. Ooi, Wei Ying Jen, Liang Piu Koh, Esther Chan, Lip Kun Tan, Yufen Goh, Wilson Wang, Bryan T. H. Koh, Chan Ming Chun, Melissa J. Fullwood, Wee Joo Chng, Motomi Osato, John Anto Pulikkan, Henry Yang, Leilei Chen, Daniel G. Tenen
Summary: Adenosine deaminases acting on RNA (ADAR) family of enzymes, especially ADAR2, play a role in multiple cancers. This study shows that ADAR2 is downregulated in certain types of acute myeloid leukemia (AML) and suppresses leukemogenesis in AML cells with t(8;21) or inv(16) translocations, through its RNA editing function.
Article
Biochemistry & Molecular Biology
Casey S. Jacobsen, Prince Salvador, John F. Yung, Sabrina Kragness, Herra G. Mendoza, Gail Mandel, Peter A. Beal
Summary: Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in duplex RNA, resulting in an effective A-to-G edit. ADAR editing can lead to recoding events and alterations in RNA function. One limitation of ADAR is its preference for editing adenosines with specific neighboring nucleotides, but new strategies and approaches are being developed to overcome this.
ACS CHEMICAL BIOLOGY
(2023)
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
Biology
Dhruva Katrekar, Yichen Xiang, Nathan Palmer, Anushka Saha, Dario Meluzzi, Prashant Mali
Summary: Adenosine deaminases acting on RNA (ADARs) have potential for programmable RNA editing, but their exogenous delivery leads to non-specific targeting and low enzymatic activity on certain RNA motifs. By performing a deep mutational scan of the ADAR2 deaminase domain, we improved enzymatic activity and developed a split-ADAR2 deaminase with significantly higher specificity for RNA editing. This systematic engineering of the ADAR2 deaminase domain has important implications for RNA biotechnology applications.
Article
Cell Biology
Winston H. Cuddleston, Xuanjia Fan, Laura Sloofman, Lindsay Liang, Enrico Mossotto, Kendall Moore, Sarah Zipkowitz, Minghui Wang, Bin Zhang, Jiebiao Wang, Nenad Sestan, Bernie Devlin, Kathryn Roeder, Stephan J. Sanders, Joseph D. Buxbaum, Michael S. Breen
Summary: This study reveals the spatiotemporal and genetic regulation of adenosine-to-inosine (A-to-I) editing in human brain development. Over 10,000 spatiotemporally regulated A-to-I sites were identified, with 37 sites recoding amino acids in protein coding regions. Hyper-edited transcripts were enriched in the aging brain and stabilized RNA secondary structures. These findings were confirmed in mouse and non-human primate models of neurodevelopment. Additionally, thousands of cis-editing quantitative trait loci (edQTLs) with unique regulatory effects were identified during prenatal and postnatal development.
Article
Oncology
Ananya Hariharan, Weihong Qi, Hubert Rehrauer, Licun Wu, Manuel Ronner, Martin Wipplinger, Jelena Kresoja-Rakic, Suna Sun, Lucia Oton-Gonzalez, Marika Sculco, Veronique Serre-Beinier, Clement Meiller, Christophe Blanquart, Jean-Francois Fonteneau, Bart Vrugt, Jan Hendrik Ruschoff, Isabelle Opitz, Didier Jean, Marc de Perrot, Emanuela Felley-Bosco
Summary: This study found increased levels of ADAR-mediated RNA editing in mesothelioma tumors and primary cultures compared to mesothelial cells. Heterogeneity in editing was observed between tumor samples and primary cultures. ADAR2 expression levels were higher in BRCA1-associated protein 1 wild-type tumors and correlated with changes in RNA editing in transcripts and 3'UTR. ADAR2 was found to play a role in cell proliferation, cell cycle, sensitivity to antifolate treatment, and type-1 interferon signaling, leading to changes in the microenvironment in vivo.
MOLECULAR ONCOLOGY
(2022)
Review
Oncology
Heming Wang, Sinuo Chen, Jiayi Wei, Guangqi Song, Yicheng Zhao
Summary: RNA editing, induced by ADAR, plays a crucial regulatory role in metazoans, affecting multiple cellular processes and functions. Despite the development of bioinformatics tools for identifying editing sites, the lack of widely accepted standards and challenges in tumor sample analysis still exist. Numerous editing sites have been reported in non-coding regions, impacting the biosynthesis of ncRNAs.
FRONTIERS IN ONCOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Juan F. Diaz F. Quiroz, Louise D. D. Siskel, Joshua J. C. Rosenthal
Summary: Adenosine deamination by ADAR enzymes edits genetic information in mRNA. Researchers have developed two systems to redirect ADAR activity for therapeutic purposes. Currently, this technology is mainly used for correcting genetic mutations, but we argue that it can be used to modulate cell physiology in a temporary manner, particularly in the nervous system, for therapeutic advantages.
Article
Multidisciplinary Sciences
Haixia Li, Jianjun Wang, Juchuanli Tu
Summary: RNA editing is a process that alters RNA sequence, with nonsynonymous editing significantly enriched in ubiquitination sites. Previous research found that lysine codons are enriched in the preferred deamination sites for RNA editing. Our study found that mRNA with edited ubiquitination sites can be translated into protein, and these editing sites showed differential editing in tumor samples and were correlated with clinical outcomes. Additionally, these genes were specifically enriched in the immune response pathway.
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)
Review
Biochemistry & Molecular Biology
Khadija Hajji, Jiri Sedmik, Anna Cherian, Damiano Amoruso, Liam P. P. Keegan, Mary A. A. O'Connell
Summary: The ADAR enzymes play important roles in neuronal function and innate immune control. This review focuses on ADAR2 proteins involved in efficient, highly site-specific RNA editing. The review covers the history of ADAR2 protein research, structural studies, disease models, and the use of ADAR RNA editing for gene therapy.
Article
Chemistry, Multidisciplinary
Anna S. Stroppel, Ruth Lappalainen, Thorsten Stafforst
Summary: By combining site-directed adenosine-to-inosine RNA editing with chemically induced dimerization, tight and dose-dependent control of editing reactions have been achieved, with up to 42% editing yields for disease-relevant mutations. This approach opens up new possibilities for basic research tools and promising clinical applications in the future.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Kanako Nose, Kota Hidaka, Takashi Yano, Yohei Tomita, Masatora Fukuda
Summary: The study developed short-chain AD-gRNA as a potential basic framework for practical RNA-editing oligonucleotides, demonstrating good editing induction activity and lower off-target editing activity.
NUCLEIC ACID THERAPEUTICS
(2021)
Article
Neurosciences
Miloslav Korinek, Vojtech Vyklicky, Jirina Borovska, Katarina Lichnerova, Martina Kaniakova, Barbora Krausova, Jan Krusek, Ales Balik, Tereza Smejkalova, Martin Horak, Ladislav Vyklicky
JOURNAL OF PHYSIOLOGY-LONDON
(2015)
Article
Multidisciplinary Sciences
Vojtech Vyklicky, Barbora Krausova, Jiri Cerny, Ales Balik, Martin Zapotocky, Marian Novotny, Katarina Lichnerova, Tereza Smejkalova, Martina Kaniakova, Miloslav Korinek, Milos Petrovic, Petr Kacer, Martin Horak, Hana Chodounska, Ladislav Vyklicky
SCIENTIFIC REPORTS
(2015)
Article
Neurosciences
Vojtech Vyklicky, Tereza Smejkalova, Barbora Krausova, Ales Balik, Miloslav Korinek, Jirina Borovska, Martin Horak, Marketa Chvojkova, Lenka Kleteckova, Karel Vales, Jiri Cerny, Michaela Nekardova, Hana Chodounska, Eva Kudova, Ladislav Vyklicky
JOURNAL OF NEUROSCIENCE
(2016)
Article
Neurosciences
Marek Ladislav, Jiri Cerny, Jan Krusek, Martin Horak, Ales Balik, Ladislav Vyklicky
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2018)
Article
Neurosciences
Andrew C. Penn, Ales Balik, Christian Wozny, Ondrej Cais, Ingo H. Greger
Article
Biochemistry & Molecular Biology
Aamira Tariq, Wojciech Garncarz, Cornelia Handl, Ales Balik, Oliver Pusch, Michael F. Jantsch
NUCLEIC ACIDS RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
Ales Balik, Andrew C. Penn, Zsofia Nemoda, Ingo H. Greger
NUCLEIC ACIDS RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
Andrew C. Penn, Ales Balik, Ingo H. Greger
NUCLEIC ACIDS RESEARCH
(2013)
Article
Biochemistry & Molecular Biology
Jiri Cerny, Paulina Bozikova, Ales Balik, Sergio M. Marques, Ladislav Vyklicky
Article
Neurosciences
Barbora Hrcka Krausova, Bohdan Kysilov, Jiri Cerny, Vojtech Vyklicky, Tereza Smejkalova, Marek Ladislav, Ales Balik, Miloslav Korinek, Hana Chodounska, Eva Kudova, Ladislav Vyklicky
JOURNAL OF NEUROSCIENCE
(2020)
Article
Neurosciences
Hana Mikova, Viktor Kuchtiak, Irena Svobodova, Veronika Spisska, Dominika Pacesova, Ales Balik, Zdenka Bendova
Summary: The study evaluated the circadian rhythmicity of AMPA receptor GluA2 subunit in the SCN and other brain structures in Wistar rats, revealing differences in expression patterns and correlations in different brain regions.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Health Care Sciences & Services
Katerina Hirschfeldova, Jiri Cerny, Paulina Bozikova, Viktor Kuchtiak, Tobias Rausch, Vladimir Benes, Filip Spaniel, David Gregus, Jiri Horacek, Ladislav Vyklicky, Ales Balik
Summary: This study investigated the genetic variability of 16 iGluR genes in schizophrenia patients, identifying significantly increased genetic variations in genes such as GRIN2A-B, GRIN3A-B, and GRIK4. Intronic haplotypes and SNPs within iGluR gene sequences were associated with schizophrenia, indicating that intronic regulatory regions play a role in genetic predisposition to schizophrenia.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Physiology
V. Vyklicky, M. Korinek, T. Smejkalova, A. Balik, B. Krausova, M. Kaniakova, K. Lichnerova, J. Cerny, J. Krusek, I. Dittert, M. Horak, L. Vyklicky
PHYSIOLOGICAL RESEARCH
(2014)
Meeting Abstract
Biophysics
B. Krausova, A. Balik, V. Vyklicky, J. Borovska, L. Vyklicky
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2013)