| Zhang Shuqin,Cui Ming,Zhang Mengran,et al.Effect of total body 137Cs γ-irradiation on the m6A modification profile of circRNA in mouse bone marrow cells[J].Chinese Journal of Radiological Medicine and Protection,2021,41(12):912-919 |
| Effect of total body 137Cs γ-irradiation on the m6A modification profile of circRNA in mouse bone marrow cells |
| Received:June 18, 2021 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.12.006 |
| KeyWords:γ-rays Bone marrow cells circRNA m6A modification Radiation injury |
| FundProject:国家自然科学基金（82173467，81803062，81730086，81872555） |
| Author Name | Affiliation | E-mail | | Zhang Shuqin | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Cui Ming | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Zhang Mengran | Novogene Co., Ltd, Beijing 100015, China | | | Li Yuan | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Xiao Huiwen | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Dong Jiali | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Shang Yue | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | | | Fan Saijun | Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China | fansaijun@irm-cams.ac.cn |
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| Abstract:: |
| Objective To investigate the effect of ionizing radiation on the N6-methyladenine (m6A) modification profile of circular RNA (circRNA) in mouse bone marrow cells and provide scientific basis for revealing the relationship between RNA epigenetic modification and hematopoietic radiation injury. Methods A total of twenty four C57BL/6 J mice were randomly divided into two groups:the healthy control group (n=12), and ionizing radiation group (n=12) irradiated in total body with 4 Gy of 137Cs γ-rays. At 5 min after irradiation, mice were killed and bone marrow cells were collected from the femur. Total RNAs were extracted and the changes in circRNA m6A modification profiles were investigated by RNA immunoprecipitation-high-throughput sequencing (MeRIP-Seq) technology and bioinformatics analysis. The representative alterations of m6A peaks were validated by MeRIP-PCR assay. Results 325 and 455 m6A sites were identified on circRNAs in the healthy control group and ionizing radiation group (178 common sites, 147 specific sites in the healthy control group and 277 specific sites in ionizing radiation group), respectively. 1 275 and 1 017 deriving genes of m6A-circRNAs were identified in the healthy control group and ionizing radiation group (767 common genes, 508 specific genes in the healthy control group and 250 specific genes in ionizing radiation group), respectively. Compared with the control healthy group, 414 (178) m6A peaks was significantly up- (down-) regulated in the ionizing radiation group(P<10-10; fold-change cut-off > 5). Moreover, Gene Ontology (GO) assay revealed that the deriving genes of circRNAs with differentially methylated m6A sites between two groups involves various functions including chromatin regulation, ciliary transition fiber and poly (A)-specific ribonuclease activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) assay revealed that the deriving genes of circRNAs with differentially methylated m6A sites between two groups included numerous pathways such as platelet activation, Fc γ R-mediated phagocytosis and B cell receptor signaling pathway. Conclusions Ionizing radiation triggers rapid alterations in the m6A modification profile of circRNA in mouse bone marrow cells. The deriving genes of differentially methylated circRNAs are associated with a variety of functions and signaling pathways of hematopoietic radiobiology. |
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