ADAR1-mediated RNA editing promotes B cell lymphomagenesis.
| Title: | ADAR1-mediated RNA editing promotes B cell lymphomagenesis. |
|---|---|
| Authors: | Pecori R; Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Helmholtz Institute for Translational Oncology (HI-TRON), Mainz, Germany.; Ren W; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Pirmoradian M; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; Wang X; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Liu D; BGI-Shenzhen, Shenzhen, China.; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China.; Berglund M; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; Li W; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Tasakis RN; Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Graduate Program in Biosciences, University of Heidelberg, Heidelberg, Germany.; Di Giorgio S; Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Ye X; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Li X; BGI-Shenzhen, Shenzhen, China.; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China.; Arnold A; Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Wüst S; Research Group 'Dynamics of Early Viral Infection and the Innate Antiviral Response', Division Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Schneider M; Proteomics Core Facility (W120), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Selvasaravanan KD; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.; Fuell Y; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.; Stafforst T; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.; Amini RM; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; Sonnevi K; Hematology Unit, Department of Medicine, Huddinge, Karolinska Institutet and Medical Unit Hematology, Karolinska University Hospital, Solna, StockholmSweden.; Enblad G; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; Sander B; Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.; Wahlin BE; Hematology Unit, Department of Medicine, Huddinge, Karolinska Institutet and Medical Unit Hematology, Karolinska University Hospital, Solna, StockholmSweden.; Wu K; BGI-Shenzhen, Shenzhen, China.; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China.; Zhang H; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; Helm D; Proteomics Core Facility (W120), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Binder M; Research Group 'Dynamics of Early Viral Infection and the Innate Antiviral Response', Division Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Papavasiliou FN; Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Graduate Program in Biosciences, University of Heidelberg, Heidelberg, Germany.; Pan-Hammarström Q; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.; BGI-Shenzhen, Shenzhen, China. |
| Source: | IScience [iScience] 2023 May 12; Vol. 26 (6), pp. 106864. Date of Electronic Publication: 2023 May 12 (Print Publication: 2023). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, [2018]- |
| Abstract: | Diffuse large B cell lymphoma (DLBCL) is one of the most common types of aggressive lymphoid malignancies. Here, we explore the contribution of RNA editing to DLBCL pathogenesis. We observed that DNA mutations and RNA editing events are often mutually exclusive, suggesting that tumors can modulate pathway outcomes by altering sequences at either the genomic or the transcriptomic level. RNA editing targets transcripts within known disease-driving pathways such as apoptosis, p53 and NF-κB signaling, as well as the RIG-I-like pathway. In this context, we show that ADAR1-mediated editing within MAVS transcript positively correlates with MAVS protein expression levels, associating with increased interferon/NF-κB signaling and T cell exhaustion. Finally, using targeted RNA base editing tools to restore editing within MAVS 3'UTR in ADAR1-deficient cells, we demonstrate that editing is likely to be causal to an increase in downstream signaling in the absence of activation by canonical nucleic acid receptor sensing.; (© 2023 The Authors.) |
| Competing Interests: | The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Epigenetics; Genetics; Molecular biology; Omics; Transcriptomics |
| Entry Date(s): | Date Created: 20230531 Latest Revision: 20230601 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10225930 |
| DOI: | 10.1016/j.isci.2023.106864 |
| PMID: | 37255666 |
| Database: | MEDLINE |
Journal Article