[1]任春艳,等.慢性社交挫败应激小鼠大脑的C-U RNA编辑[J].深圳大学学报理工版,2021,38(5):510-516.[doi:10.3724/SP.J.1249.2021.05510]
 REN Chunyan,,et al.C-U RNA editing in the mouse brain under chronic social defeat stress[J].Journal of Shenzhen University Science and Engineering,2021,38(5):510-516.[doi:10.3724/SP.J.1249.2021.05510]
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慢性社交挫败应激小鼠大脑的C-U RNA编辑()
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《深圳大学学报理工版》[ISSN:1000-2618/CN:44-1401/N]

卷:
第38卷
期数:
2021年第5期
页码:
510-516
栏目:
生物工程
出版日期:
2021-09-15

文章信息/Info

Title:
C-U RNA editing in the mouse brain under chronic social defeat stress
文章编号:
202105010
作者:
任春艳1 2 3魏志远1 3饶军华4饶义剑2陈建欢1 3
1)江南大学无锡医学院,江苏无锡 214122
2)江南大学生物工程学院,江苏无锡214122
3)江南大学-广东科学院动物研究所“慢性病灵长类研究联合实验室”,江苏无锡214122
4)广东科学院动物研究所,广东广州510260
Author(s):
REN Chunyan1 2 3 WEI Zhiyuan1 3 RAO Junhua4 RAO Yijian2 and CHEN Jianhuan1 3
1) Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu Province, P.R.China
2) School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu Province, P.R.China
3) Joint Primate Research Center for Chronic Diseases of Jiangnan University & Institute of Zoology of Guangdong Academy of Sciences, Jiangnan University, Wuxi 214122, Jiangsu Province, P.R.China
4) Institute of Zoology of Guangdong Academy of Sciences, Guangzhou 510260, Guangdong Province, P.R.China
关键词:
神经生物学核糖核酸编辑社交挫败情绪应激生理应激腹侧被盖区抑郁创伤后应激障碍
Keywords:
neurobiology RNA editing social defeat emotional stress physical stress ventral tegmental area depression post-traumatic stress disorder
分类号:
Q819; R749
DOI:
10.3724/SP.J.1249.2021.05510
文献标志码:
A
摘要:
核糖核酸(ribonucleic acid, RNA)编辑与应激、神经系统疾病和精神疾病有关,然而胞苷到尿苷(C-U)的 RNA编辑与慢性社交挫败应激(chronic social defeat stress, CSDS)的相关性尚未明确.分析小鼠大脑奖赏关键区——腹侧被盖区(ventral tegmental area, VTA)中存在的C-U编辑,及其在情绪应激(emotional stress, ES)或生理应激(physical stress, PS)下的社交挫败模型中的变化.结果发现,在成年雄性小鼠VTA内约16 198个高置信度编辑位点存在C-U编辑.其中,48个位点具有显著组间差异RNA编辑水平,其主成分分析显示,主成分1的贡献率达到了51.78%.此外,ES组、PS组和对照组中分别有307、223和301个位点特异地存在于组内的多个样本中,并在与中枢神经系统相关的基因功能方面呈现差异化的富集.更重要的是,作为应激的重要相关因子,血清和糖皮质激素依赖性激酶1基因在ES组中特异性地表达显著上调,同时其mRNA也在ES中存在特异的编辑.研究结果证明,CSDS小鼠模型大脑VTA中存在明确的C-U RNA编辑改变,且可能参与CSDS相关的潜在分子机制.
Abstract:
Existing studies suggest that RNA editing is associated with stress, neurological diseases and psychiatric disorders. However, the role of C-U RNA editing in chronic social defeat stress (CSDS) remains unclear. The current study herein analyzed mRNA C-U editing in the brain ventral tegmental area (VTA), a key brain reward region, and its changes in mouse models of CSDS under emotional stress (ES) or physiological stress (PS) conditions compared to controls. Our results discovered and validated C-U editing at 16 198 high confidence editing sites in adult male mouse VTA. Among them, 48 sites showed differential RNA editing levels among the three groups. Principal component analysis revealed 51.78% contribution from principle component 1 (PC1) to the variance. In addition, there were 307, 223, and 301 sites repeatedly observed in intra-group samples in ES, PS and control groups, respectively, and which were enriched in different gene functions. Moreover, a key factor previously reported to be involved in stress, serum/glucocorticoid regulated kinase 1 (Sgk1) gene was specifically upregulated and its mRNA was also specifically edited in ES. These results demonstrate dynamic C-U RNA editing in the brain VTA of mouse models of CSDS, which further suggests that C-U RNA editing is a potential molecular mechanism related to CSDS.

参考文献/References:

[1] BLANC V, DAVIDSON N O. C-to-U RNA editing: mechanisms leading to genetic diversity[J]. Journal of Biological Chemistry, 2003, 278(3): 1395-1398.
[2] SILBERBERG G, LUNDIN D, NAVON R, et al. Deregulation of the A-to-I RNA editing mechanism in psychiatric disorders[J]. Human Molecular Genetics, 2012, 21(2): 311-321.
[3] BREEN M S, DOBBYN A, LI Qin, et al. Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia[J]. Nature Neuroscience, 2019, 22(9): 1402-1412.
[4] WARREN B L, VIALOU V F, INIGUEZ S D, et al. Neurobiological sequelae of witnessing stressful events in adult mice[J]. Biological Psychiatry, 2013, 73(1): 7-14.
[5] DICK A L W, KHERMESH K, PAUL E, et al. Adenosine-to-Inosine RNA editing within corticolimbic brain regions is regulated in response to chronic social defeat stress in mice[J]. Frontiers in Psychiatry, 2019(10):277.
[6] PENA C J, KRONMAN H G, WALKER D M, et al. Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2[J]. Science, 2017, 356(6343): 1185-1188.
[7] PENA C J, SMITH M, RAMAKRISHNAN A, et al. Early life stress alters transcriptomic patterning across reward circuitry in male and female mice[J]. Nature Communications, 2019, 10(1): 5098.
[8] DOBIN A, DAVIS C A, SCHLESINGER F, et al. STAR: ultrafast universal RNA-seq aligner[J]. Bioinformatics, 2013, 29(1): 15-21.
[9] LI H, HANDSAKER B, WYSOKER A, et al. The sequence alignment/map format and SAMtools[J]. Bioinformatics, 2009, 25(16): 2078-2079.
[10] VAN DER AUWERA G A, CARNEIRO M O, HARTL C, et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline[J]. Current Protocols in Bioinformatics, 2013, 43(1110):11.10.1-11.10.33.
[11] KOBOLDT D C, ZHANG Q, LARSON D E, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing[J]. Genome Research, 2012, 22(3): 568-576.
[12] BAHN J H, LEE J H, LI Gang, et al. Accurate identification of A-to-I RNA editing in human by transcriptome sequencing[J]. Genome Research, 2012, 22(1): 142-150.
[13] MCLAREN W, GIL L, HUNT S E, et al. The ensembl variant effect predictor[J]. Genome Biology, 2016, 17(1): 122.
[14] MCCARTHY D J, CHEN Y, SMYTH G K. Differential expression analysis of multifactor RNA-seq experiments with respect to biological variation[J]. Nucleic Acids Research, 2012, 40(10): 4288-4297.
[15] KULESHOV M V, JONES M R, ROUILLARD A D, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update[J]. Nucleic Acids Research, 2016, 44(W1): W90-W97.
[16] BAIK J H. Stress and the dopaminergic reward system[J]. Experimental and Molecular Medicine, 2020, 52(12): 1879-1890.
[17] RAYON-ESTRADA V, HARJANTO D, HAMILTON C E, et al. Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(50): 13296-13301.
[18] CHAUMETTE B, FERRAFIAT V, AMBALAVANAN A, et al. Missense variants in atp1a3 and fxyd gene family are associated with childhood-onset schizophrenia[J]. Molecular Psychiatry, 2020, 25(4): 821-830.
[19] COLE D C, CHUNG Y, GAGNIDZE K, et al. Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS pathophysiology[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(50): 13272-13277.
[20] ZHOU Hang, CHENG Zhongshan, BASS N, et al. Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression[J]. Translational Psychiatry, 2018, 8(1): 208.
[21] STELLOS K, GATSIOU A, STAMATELOPOULOS K, et al. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation[J]. Nature Medicine, 2016, 22(10): 1140-1150.
[22] FILIPPINI A, BONINI D, LA VIA L, et al. The good and the bad of glutamate receptor RNA editing[J]. Molecular Neurobiology, 2017, 54(9): 6795-6805.
[23] DATTILO V, AMATO R, PERROTTI N, et al. The emerging role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in major depressive disorder: hypothesis and mechanisms[J]. Frontiers in Genetics, 2020, 11:826.
[24] ANACKER C, CATTANEO A, MUSAELYAN K, et al. Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(21): 8708-8713.

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备注/Memo

备注/Memo:
Received:2021-02-18;Accepted:2021-03-15;Online(CNKI):2021-06-21
Foundation:National Natural Science Foundation of China (31671311); Natural Science Foundation of Guangdong Province(2019A1515012062); The Fundamental Research Foundation for the Central Universities(JUSRP51712B,JUSRP1901XNC)
Corresponding author:Professor CHEN Jianhuan. E-mail: cjh_bio@hotmail.com
Citation:REN Chunyan, WEI Zhiyuan, RAO Junhua, et al. C-U RNA editing in the mouse brain under chronic social defeat stress[J]. Journal of Shenzhen University Science and Engineering, 2021, 38(5): 510-516.(in Chinese)
基金项目:国家自然科学基金资助项目(31671311);广东省自然科学基金资助项目(2019A1515012062);中央高校基本科研业务费专项资金(JUSRP51712B,JUSRP1901XNC);江南大学研究生培养创新工程项目 (KYCX20_1946);无锡“太湖人才计划”创新领军人才项目
作者简介:任春艳(1995—),江南大学硕士研究生.研究方向:RNA编辑酶的功能研究及其应用.
E-mail: renchunyan950124@163.com
引文:任春艳,魏志远,饶军华,等.慢性社交挫败应激小鼠大脑的C-U RNA编辑[J]. 深圳大学学报理工版,2021,38(5):510-516.
更新日期/Last Update: 2021-09-30