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创伤性脑损伤后小鼠海马中改变的 m6A 标记转录谱的全基因组筛选。

Genome-wide screening of altered m6A-tagged transcript profiles in the hippocampus after traumatic brain injury in mice.

机构信息

CNRS-LIA Hematology and Cancer, Sino-French Research Center for Life Sciences & Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, PR China.

Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.

出版信息

Epigenomics. 2019 May;11(7):805-819. doi: 10.2217/epi-2019-0002. Epub 2019 Mar 18.

DOI:10.2217/epi-2019-0002
PMID:30882247
Abstract

To systematically profile RNA m6A modification landscape after traumatic brain injury (TBI) in mice. Expression of m6A-related genes was detected by quantitative real-time PCR (qPCR). Expression and location of METTL3, a key component of m6A methyltransferase complex, were determined by immunostaining. Genome-wide profiling of m6A-tagged transcripts was conducted by m6A-modified RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq). METTL3 was downregulated after TBI. In total, 922 m6A peaks were differentially expressed as determined by m6A-RIP-seq, with 370 upregulated and 552 downregulated. In addition, we identified differentially expressed hypomethylated and hypermethylated mRNA transcripts. Our data provided novel information regarding m6A modification changes in the early period of TBI, which might be promising therapy targets.

摘要

目的

系统分析创伤性脑损伤(TBI)后小鼠的 RNA m6A 修饰图谱。采用实时定量 PCR(qPCR)检测 m6A 相关基因的表达。免疫染色法检测 m6A 甲基转移酶复合物关键成分 METTL3 的表达和定位。采用 m6A 修饰 RNA 免疫沉淀测序(m6A-RIP-seq)和 RNA 测序(RNA-seq)进行全基因组 m6A 标记转录本的分析。结果:TBI 后 METTL3 下调。m6A-RIP-seq 检测到 922 个差异表达的 m6A 峰,其中 370 个上调,552 个下调。此外,我们还鉴定了差异表达的低甲基化和高甲基化 mRNA 转录本。结论:本研究为 TBI 早期 m6A 修饰变化提供了新信息,可能是有前途的治疗靶点。

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