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)
Review
Biochemistry & Molecular Biology
Anton O. Goncharov, Victoria O. Shender, Ksenia G. Kuznetsova, Anna A. Kliuchnikova, Sergei A. Moshkovskii
Summary: Adenosine-to-inosine RNA editing is a widespread post-transcriptional modification system catalyzed by ADAR enzymes, which mainly occurs in dsRNA before splicing. This review focuses on the interconnections between RNA editing and splicing in human cancer. Dysregulated RNA splicing in cancer can lead to the release of excess dsRNA into the cytosol, triggering antiviral-like responses and potentially inhibiting tumor growth. Inhibiting ADAR may enhance the effects of spliceosome inhibitors and could be a promising approach in cancer therapies targeting RNA splicing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Nikolaos Vlachogiannis, Simon Tual-Chalot, Eleftherios Zormpas, Francesca Bonini, Panagiotis A. Ntouros, Maria Pappa, Vasiliki-Kalliopi Bournia, Maria G. Tektonidou, Vassilis L. Souliotis, Clio P. Mavragani, Kimon Stamatelopoulos, Aikaterini Gatsiou, Petros P. Sfikakis, Konstantinos Stellos
Summary: This study demonstrates that ADAR1p150-mediated A-to-I RNA editing is critically involved in type I IFN responses in systemic sclerosis patients, highlighting the importance of post-transcriptional regulation in proinflammatory gene expression in autoimmune diseases such as SSc.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Respiratory System
Kevin M. Magnaye, Katherine A. Naughton, Janel Huffman, D. Kyle Hogarth, Edward T. Naureckas, Steven R. White, Carole Ober
Summary: This study identified reduced A-to-I editing of miR-200b-3p at the 5th position in lower airway cells from moderate-to-severe asthmatics, leading to overexpression of SOCS1 and impaired cytokine signaling. ADAR-mediated editing may contribute to features of moderate-to-severe asthma in adulthood.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Yoav Shoshan, Noa Liscovitch-Brauer, Joshua J. C. Rosenthal, Eli Eisenberg
Summary: RNA editing by ADAR enzymes converts adenosines into inosines, altering protein-coding sequences and diversifying the proteome; recoding is abundant in neural tissues of coleoid cephalopods with over-representation of nonsynonymous edits; shared, strongly recoded sites in coleoids have been selected for proteome diversification, suggesting that an editable A is more beneficial than an uneditable A or a genomically encoded G.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Cell Biology
David Rodriguez Morales, Mirolyuba Ilieva, Sarah Rennie, Shizuka Uchida
Summary: Adenosine to inosine (A-to-I) RNA editing is a common RNA modification in mammalian transcriptomes. Upregulated RNA editing enzymes, adenosine deaminase acting on RNAs (ADARs), suggest that monitoring RNA editing patterns could be useful as diagnostic biomarkers for diseases. This article provides an overview of epitranscriptomics and focuses on the detection and analysis of A-to-I RNA editing using bioinformatic tools in RNA-seq data sets, while briefly reviewing its involvement in disease progressions. The authors argue for routine detection of RNA editing patterns in RNA-based data sets to accelerate the identification of disease-related RNA editing targets.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chia-Yu Shih, Yun-Chi Chen, Heng-Yi Lin, Chia-Ying Chu
Summary: The DEAD-box proteins, including DDX6, are RNA-binding proteins that play a role in post-transcriptional regulation of gene expression. DDX6 has functions in translational repression, miRNA-mediated gene silencing, and RNA decay in the cytoplasm. Its nuclear function was previously unknown until this study discovered its interaction with ADAR1, a protein involved in RNA editing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Nicolas Salvetat, Fabrice Chimienti, Christopher Cayzac, Benjamin Dubuc, Francisco Checa-Robles, Pierrick Dupre, Sandie Mereuze, Vipul Patel, Catherine Genty, Jean-Philippe Lang, Jean-Francois Pujol, Philippe Courtet, Dinah Weissmann
Summary: The study found significant alterations in RNA editing of the PDE8A gene in the blood of patients with major depressive disorder and suicide attempters, suggesting a link to inflammation, cognition, and antidepressant treatment. Monitoring RNA editing in PDE8A in blood samples may help evaluate depressive state and suicide risk.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Yulong Song, Xiuju He, Wenbing Yang, Yaoxing Wu, Jun Cui, Tian Tang, Rui Zhang
Summary: This study developed an editing identification pipeline specifically for RNA viruses and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2 from diverse samples. The findings showed that A-to-I editing was dynamically regulated, varied between tissue and cell types, and correlated with the intensity of innate immune response. Additionally, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. The study also provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans during the epidemic.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Tram Anh Nguyen, Jia Wei Joel Heng, Yan Ting Ng, Rui Sun, Shira Fisher, Gokce Oguz, Pornchai Kaewsapsak, Shifeng Xue, Bruno Reversade, Adaikalavan Ramasamy, Eli Eisenberg, Meng How Tan
Summary: This study identified millions of editing events in Xenopus with high accuracy and systematically mapped the editome across developmental stages, adult organs, and species. The highest deamination activity was observed in early embryogenesis and in the ovary. Editing events showed poor conservation across different Xenopus species. The findings suggest that species-specific editing may play a role in the unique physiology or environmental adaptation of each animal.
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
Toxicology
Akin Cayir
Summary: Epigenetic modifications, including RNA editing, can be influenced by environmental stimuli and are linked with adverse health outcomes; over 150 reversible RNA modifications have been identified, indicating dynamic features of modification; the RNA editing field is expanding and requires more empirical evidence for diseases and toxicology.
CRITICAL REVIEWS IN TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huimin Zhu, Lu Huang, Songbin Liu, Zhiming Dai, Zhou Songyang, Zhihui Weng, Yuanyan Xiong
Summary: This paper presents REIA, an interactive web server for analyzing and visualizing the association between human cancers and A-to-I RNA editing sites. REIA offers various options to browse annotation/editing levels and compare differences between editing and non-editing groups.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemical Research Methods
Xilei Ai, Shan Zhou, Meiyi Chen, Feng Du, Yi Yuan, Xin Cui, Juan Dong, Xin Huang, Zhuo Tang
Summary: RNA editing is a reversible therapeutic approach for correcting pathogenic mutations. This study presents a small molecule-inducible RNA editing strategy by incorporating aptazymes into ADAR-based RNA editing technology. The aptazymes trigger self-cleavage in the presence or absence of small molecules, allowing controlled RNA editing. This strategy improves the safety and potential clinical applications of RNA editing technology.
ACS SYNTHETIC BIOLOGY
(2023)
Review
Oncology
Gioacchino P. Marceca, Luisa Tomasello, Rosario Distefano, Mario Acunzo, Carlo M. Croce, Giovanni Nigita
Summary: A-to-I editing in RNA plays a crucial role in cancer biology, affecting miRNA function with clinical significance. Challenges remain in identifying and characterizing miRNA editing events in tumors.
Article
Oncology
Franz J. Gassner, Nadja Zaborsky, Ilana Buchumenski, Erez Y. Levanon, Matthias Gatterbauer, Maria Schubert, Stefanie Rauscher, Daniel Hebenstreit, Ferran Nadeu, Elias Campo, Alexander Egle, Richard Greil, Roland Geisberger
Summary: Research suggests that RNA editing plays a significant role in chronic lymphocytic leukemia (CLL), affecting patient prognosis and cellular drug resistance. Targeting the RNA editing machinery could be a future strategy to maximize treatment efficacy for CLL patients.
Article
Multidisciplinary Sciences
Yuange Duan, Shengqian Dou, Hagit T. Porath, Jiaxing Huang, Eli Eisenberg, Jian Lu
Summary: Social insects exhibit extensive phenotypic diversities, suggesting a role for epigenetic regulations beyond the genome level. ADAR-mediated RNA editing expands proteomic diversities and facilitates adaptive evolution. In honeybees, editing is most abundant in the heads, with differences in editing behavior between different castes, indicating a role in caste differentiation.
Article
Psychiatry
Gal Warhaftig, Chaya Mushka Sokolik, Khen Khermesh, Yehuda Lichtenstein, Michal Barak, Tzofnat Bareli, Erez Y. Levanon, Gal Yadid
Summary: The study found changes in the RNA editing machinery in the central amygdala associated with PTSD, and deamination of the 5-HT2C serotonin receptor may help alleviate PTSD-like behaviors. This research provides a new avenue for understanding PTSD regulation.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ilana Buchumenski, Karoline Holler, Lior Appelbaum, Eli Eisenberg, Jan Philipp Junker, Erez Y. Levanon
Summary: A-to-I RNA editing, mediated by ADAR enzymes, increases transcript and protein diversity. Studying zebrafish editing sites revealed high editing levels in early embryos and reproductive organs, providing insights into editing roles during development and maturity.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Ophthalmology
Nina Schneider, Yogapriya Sundaresan, Prakadeeswari Gopalakrishnan, Avigail Beryozkin, Mor Hanany, Eyal Banin, Shay Ben-Aroya, Dror Sharon
Summary: Inherited retinal diseases (IRDs) are a complex and heterogeneous group of visual impairments caused by pathogenic variants in numerous genes. The understanding of the genotype-phenotype correlations, inheritance patterns, hypomorphic alleles, and modifier genes associated with IRDs is challenging due to their unique characteristics. Advances in next-generation sequencing have facilitated the identification of novel IRD-related genes and variants. The Global Retinal Inherited Disease (GRID) dataset provides valuable information on the frequencies and complexities of pathogenic variants among 194 genes.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Orshay Gabay, Yoav Shoshan, Eli Kopel, Udi Ben-Zvi, Tomer D. Mann, Noam Bressler, Roni Cohen-Fultheim, Amos A. Schaffer, Shalom Hillel Roth, Ziv Tzur, Erez Y. Levanon, Eli Eisenberg
Summary: Gabay et al. presented a highly accurate atlas of A-to-I RNA editing in humans, covering editing sites across different tissues and cell subpopulations. Most edited sites are evolutionarily conserved in non-primate mammals, indicating adaptation. Editing by adenosine deaminases alters mRNA encoded information, affecting protein-coding sequences and diversifying the proteome.
NATURE COMMUNICATIONS
(2022)
Article
Public, Environmental & Occupational Health
Michal Solomon, Ariel Gimple, Inbal Fuchs, Assi Cicurel, Tal Meninger, Dror Avni, Abed Nasereddin, Charles L. Jaffe, Eli Schwartz
Summary: The study aimed to investigate the prevalence of Leishmania in the blood of patients with active or previous cutaneous leishmaniasis (CL). The findings of this pilot study suggest that people with active or recent CL caused by L. major and L. tropica do not harbor parasites in their blood. Hence, their exclusion from blood donation should be revisited.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Biochemistry & Molecular Biology
Moamen Masalha, Tal Meningher, Adi Mizrahi, Aviv Barzilai, Hilla Tabibian-Keissar, Devorah Gur-Wahnon, Iddo Z. Ben-Dov, Joshua Kapenhas, Jasmine Jacob-Hirsch, Raya Leibowitz, Yechezkel Sidi, Dror Avni
Summary: Cutaneous squamous cell carcinoma (CSCC) is a skin cancer that evolves from normal epidermis and is characterized by the disruption of cell-cell contacts and acquisition of a mesenchymal motile phenotype. The decreased expression of miR-199a-3p plays a crucial role in this process by targeting RAP2B and inhibiting the epithelial-to-mesenchymal transition (EMT). Inhibitors of RAP2B or FAK may be potential therapeutic agents for CSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dermatology
Miriam Karmon, Eli Kopel, Aviv Barzilai, Polina Geva, Eli Eisenberg, Erez Y. Levanon, Shoshana Greenberger
Summary: Atopic dermatitis (AD) is associated with reduced adenosine-to-inosine RNA editing, leading to impairment of the innate immune response and dysregulated type 1 interferon-mediated responses. This alteration in editing may play a role in the pathogenesis of AD as well as other autoimmune and inflammatory diseases, while not being observed in conditions like systemic lupus erythematosus and systemic sclerosis with IFN activation.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemical Research Methods
Tomer D. Mann, Eli Kopel, Eli Eisenberg, Erez Y. Levanon
Summary: Adenosine-to-inosine RNA editing is essential for immune regulation and is associated with various pathological conditions. In this study, the authors characterized RNA editing in the heart and arteries and found increased editing in patients with atherosclerosis, cardiomyopathies, and heart failure. They identified a specific editing site in the IGFBP7 gene that is consistently elevated in these patients. These findings highlight the importance of RNA editing in cardiovascular diseases.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Genetics & Heredity
Rona Merdler-Rabinowicz, David Gorelik, Jiwoon Park, Cem Meydan, Jonathan Foox, Miriam Karmon, Hillel S. Roth, Roni Cohen-Fultheim, Galit Shohat-ophir, Eli Eisenberg, Eytan Ruppin, Christopher E. Mason, Erez Y. Levanon
Summary: This study analyzed the RNA sequences of COVID-19 infected individuals and observed a significant increase in global RNA editing activity in COVID-19 patients. The study also identified specific coding sites with higher editing activity and found that the increase in editing activity during the disease was temporary, returning to baseline levels after symptoms disappeared. These epigenetic changes may contribute to the immune system response and affect adverse outcomes in post-viral cases.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Article
Immunology
Michal Solomon, Nadav Astman, Karin Warshavsky, Aviv Barzilai, Tal Meningher, Dror Avni, Eli Schwartz
Summary: This article reports 8 cases of Leishmania infantum cutaneous leishmaniasis in Israel, with 7 cases occurring during 2020-2021, suggesting that L. infantum may be an emerging infection in Israel.
EMERGING INFECTIOUS DISEASES
(2023)
