iScience (Jun 2023)
ADAR1-mediated RNA editing promotes B cell lymphomagenesis
- Riccardo Pecori,
- Weicheng Ren,
- Mohammad Pirmoradian,
- Xianhuo Wang,
- Dongbing Liu,
- Mattias Berglund,
- Wei Li,
- Rafail Nikolaos Tasakis,
- Salvatore Di Giorgio,
- Xiaofei Ye,
- Xiaobo Li,
- Annette Arnold,
- Sandra Wüst,
- Martin Schneider,
- Karthika-Devi Selvasaravanan,
- Yvonne Fuell,
- Thorsten Stafforst,
- Rose-Marie Amini,
- Kristina Sonnevi,
- Gunilla Enblad,
- Birgitta Sander,
- Björn Engelbrekt Wahlin,
- Kui Wu,
- Huilai Zhang,
- Dominic Helm,
- Marco Binder,
- F. Nina Papavasiliou,
- Qiang Pan-Hammarström
Affiliations
- Riccardo Pecori
- Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany; Helmholtz Institute for Translational Oncology (HI-TRON), Mainz, Germany
- Weicheng Ren
- 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
- Mohammad Pirmoradian
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
- Xianhuo Wang
- 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
- Dongbing Liu
- BGI-Shenzhen, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China
- Mattias Berglund
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Wei Li
- 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
- Rafail Nikolaos Tasakis
- Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany; Graduate Program in Biosciences, University of Heidelberg, Heidelberg, Germany
- Salvatore Di Giorgio
- Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Xiaofei Ye
- 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
- Xiaobo Li
- BGI-Shenzhen, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China
- Annette Arnold
- Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Sandra Wüst
- Research Group ''Dynamics of Early Viral Infection and the Innate Antiviral Response'', Division Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Martin Schneider
- Proteomics Core Facility (W120), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Karthika-Devi Selvasaravanan
- Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
- Yvonne Fuell
- Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
- Thorsten Stafforst
- Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
- Rose-Marie Amini
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Kristina Sonnevi
- Hematology Unit, Department of Medicine, Huddinge, Karolinska Institutet and Medical Unit Hematology, Karolinska University Hospital, Solna, StockholmSweden
- Gunilla Enblad
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Birgitta Sander
- Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- Björn Engelbrekt Wahlin
- Hematology Unit, Department of Medicine, Huddinge, Karolinska Institutet and Medical Unit Hematology, Karolinska University Hospital, Solna, StockholmSweden
- Kui Wu
- BGI-Shenzhen, Shenzhen, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen, China
- Huilai Zhang
- 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; Corresponding author
- Dominic Helm
- Proteomics Core Facility (W120), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Marco Binder
- Research Group ''Dynamics of Early Viral Infection and the Innate Antiviral Response'', Division Virus-Associated Carcinogenesis (F170), German Cancer Research Center (DKFZ), Heidelberg, Germany
- F. Nina Papavasiliou
- Division of Immune Diversity (D150), German Cancer Research Center (DKFZ), Heidelberg, Germany; Graduate Program in Biosciences, University of Heidelberg, Heidelberg, Germany; Corresponding author
- Qiang Pan-Hammarström
- 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; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 6
p. 106864
Abstract
Summary: 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.