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
Multidisciplinary Sciences
Yusuke Shiromoto, Masayuki Sakurai, Moeko Minakuchi, Kentaro Ariyoshi, Kazuko Nishikura
Summary: The study shows that the nuclear isoform p110 of ADAR1 regulates R loop formation and genome stability at telomeres in cancer cells. Editing of A-C mismatches by ADAR1p110 assists in resolving telomeric R loops, crucial for the proliferation of telomerase-positive cancer cells. These findings highlight the pro-oncogenic nature of ADAR1p110 and identify ADAR1 as a promising therapeutic target for telomerase positive cancers.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Renata Kleinova, Vinod Rajendra, Alina F. Leuchtenberger, Claudio Lo Giudice, Cornelia Vesely, Utkarsh Kapoor, Andrea Tanzer, Sophia Derdak, Ernesto Picardi, Michael F. Jantsch
Summary: ADAR1 is involved in A-to-I conversion in RNA, with two isoforms ADAR1p150 and ADAR1p110 expressed in the cytoplasm and nucleus respectively. Mutations in ADAR1 cause Aicardi - Goutieres syndrome, while deletion of ADAR1p150 leads to embryonic lethality in mice. These findings highlight the critical role of ADAR1p150 in A-to-I editing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tony Sun, Yingpu Yu, Xianfang Wu, Ashley Acevedo, Ji-Dung Luo, Jiayi Wang, William M. Schneider, Brian Hurwitz, Brad R. Rosenberg, Hachung Chung, Charles M. Rice
Summary: Defective ADAR1 editing can lead to disorders, with the two protein isoforms p150 and p110 showing different contributions to RNA editing. The challenges in expressing p150 without p110 may explain the differences in editing landscape between the two isoforms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Anna Uzonyi, Ronit Nir, Ofir Shliefer, Noam Stern-Ginossar, Yaron Antebi, Yonatan Stelzer, Erez Y. Levanon, Schraga Schwartz
Summary: Large-scale systematic probing of synthetic constructs revealed two structural layers determining the formation and propagation of A-to-I editing, independent of sequence. Editing is robustly induced at fixed intervals upstream and downstream of structural disruptions, and editing is symmetrically introduced on opposite sites of a double-stranded structure.
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
Biochemistry & Molecular Biology
Hideki Terajima, Mijia Lu, Linda Zhang, Qi Cui, Yanhong Shi, Jianrong Li, Chuan He
Summary: Research shows that m(6)A modification promotes ADAR1 expression, with YTHDF1 mediating the up-regulation of ADAR1. YTHDF1 deficiency affects IFN responses and virus replication in cells. These findings suggest a role for m(6)A and YTHDF1 in modulating innate immune responses through ADAR1-mediated A-to-I RNA editing.
Article
Cell Biology
Jia Song, Yang Liu, Yue Yin, Hui Wang, Xin Zhang, Yang Li, Xuyang Zhao, Guangze Zhang, Xiangyan Meng, Yan Jin, Dan Lu, Yuxin Yin
Summary: Cancer evades immune surveillance by inducing an immune suppressor called PTIR1, which blocks leukocyte recruitment and inhibits immunoproteasome activity, leading to immune escape and resistance to immunotherapeutic treatments. PTIR1 is induced through alternative splicing of DDX58 (RIG-I) and is activated by ADAR1, suggesting potential targets for cancer immunotherapy.
Review
Oncology
Di Lu, Jianxi Lu, Qiuli Liu, Qi Zhang
Summary: Stem cells play a critical role in organism development and tissue homeostasis. Recent studies have shown that RNA editing, mainly mediated by ADAR1, controls stem cell fate and function. ADAR1 is a multifunctional protein involved in embryonic development, cell differentiation, immune regulation, and gene editing technologies. This review summarizes the structure and function of ADAR1, with a focus on its role in stem cell self-renewal and differentiation. Targeting ADAR1 has emerged as a potential therapeutic strategy for both normal and dysregulated stem cells.
BIOMARKER RESEARCH
(2023)
Article
Cell Biology
Wei Huang, Yu-Meng Sun, Qi Pan, Ke Fang, Xiao-Tong Chen, Zhan-Cheng Zeng, Tian-Qi Chen, Shun-Xin Zhu, Li-Bin Huang, Xue-Qun Luo, Wen-Tao Wang, Yue-Qin Chen
Summary: This study identifies a novel snoRNA-related lncRNA, LNC-SNO49AB, with unique structures. The researchers found that LNC-SNO49AB is highly expressed in leukemia patients and its silencing dramatically suppresses leukemia progression. LNC-SNO49AB mainly localizes in the nucleolus and interacts with the nucleolar protein fibrillarin. It was also discovered that LNC-SNO49AB regulates genome-wide RNA A-to-I editing by enhancing ADAR1 dimerization, particularly affecting cell cycle pathways.
Article
Multidisciplinary Sciences
Nicholas W. Hubbard, Joshua M. Ames, Megan Maurano, Lan H. Chu, Kim Y. Somfleth, Nandan S. Gokhale, Margo Werner, Jessica M. Snyder, Katrina Lichauco, Ram Savan, Daniel B. Stetson, Andrew Oberst
Summary: The RNA-editing enzyme ADAR1 inhibits innate immune activation and pathology by disrupting the duplex structure of endogenous double-stranded RNA species. Alteration of the Z-DNA-binding domain (ZBD) of ADAR1 leads to activation of ZBP1, causing autoinflammatory pathology.
Review
Biology
Valentina Tassinari, Cristina Cerboni, Alessandra Soriani
Summary: ADAR1 mediates immune response modulation by A-to-I editing, preventing the development of autoimmune diseases and cancer. The activity of ADAR1 prevents the recognition of endogenous dsRNA by cellular sensors, avoiding excessive inflammation and IFN-I production.
Review
Cell Biology
Brian Song, Yusuke Shiromoto, Moeko Minakuchi, Kazuko Nishikura
Summary: ADAR1 catalyzes the conversion of adenosine to inosine in double-stranded RNA, affecting important biological processes within cells and playing roles in autoimmune diseases, cancer, and viral infections.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
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
Ting Zhang, Chaoran Yin, Aleksandr Fedorov, Liangjun Qiao, Hongliang Bao, Nazar Beknazarov, Shiyu Wang, Avishekh Gautam, Riley M. Williams, Jeremy Chase Crawford, Suraj Peri, Vasily Studitsky, Amer A. Beg, Paul G. Thomas, Carl Walkley, Yan Xu, Maria Poptsova, Alan Herbert, Siddharth Balachandran
Summary: ADAR1 is a determinant of resistance to ICB therapy by repressing immunogenic dsRNA and Z-RNA. CBL0137 is a small molecule that activates ZBP1, reverses ICB unresponsiveness, and induced necroptosis.
