基于新型DNA自组装光亲和探针鉴定mRNA甲基化修饰识别蛋白及其功能研究
批准号:
22004091
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
柏雪
依托单位:
学科分类:
分离与分析
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
柏雪
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中文摘要
mRNA修饰改变mRNA结构,并参与调控mRNA生命周期几乎所有生理过程,其调控异常会导致肿瘤等疾病的发生。招募特异性的识别蛋白激活调控通路是mRNA修饰发挥功能的重要途径,相关蛋白的鉴定是理解mRNA修饰功能的关键。由于修饰介导的mRNA-蛋白作用力较弱、动态变化,且受高丰度非特异性蛋白的干扰,mRNA修饰识别蛋白的鉴定是当前非常具有挑战性的课题。本项目拟结合DNA自组装和光交联技术,以常见的N6-methyladenosine(m6A)为模板,构建高灵敏度、高选择性的化学探针,发展mRNA修饰结合蛋白的分离分析新方法。利用该方法着重开展当前最新报道的N7-methylguanosine(m7G)识别蛋白的鉴定,并进行验证及功能探究,期待从识别蛋白入手探索m7G介导的调控过程,拓展对这一修饰功能的深入理解。该项目对于揭示mRNA修饰介导的表观遗传分子事件的调控机制具有重要的科学意义。
英文摘要
Chemical modifications in mRNA will change the structure of mRNA and participate in the regulation of almost all stages of the mRNA life cycle. The abnormal regulation can lead to the occurrence of tumor and other diseases. mRNA modification activates the regulatory pathways by recruiting specific reader proteins, so the identification of related effector proteins is the key to understand the regulatory mechanism of mRNA modification. However, Owing to the weak and dynamic RNA-protein interactions and the interference of highly abundant nonspecific proteins, the identification of the reader proteins of mRNA is still a very challenging topic. This project, combined DNA self-assembly and photo-affinity cross-linking technology and used the common N6-methyladenosine (m6A) modification as a model, intends to construct a highly sensitive and selective chemical probe, and to develop a new analytical method for the separation and analysis of mRNA modification binding proteins. This method was applied on screening and functional characterization of protein complexes recruited by the novel available N7-methylguanosine (m7G) modification, aiming at exploring the regulatory process mediated by m7G and expand the in-depth understanding of this mRNA mark from the perspective of effector proteins. The project has important research significance for revealing the regulation mechanism of epigenetic molecular events mediated by mRNA modifications.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
YiaC and CobB regulate lysine lactylation in Escherichia coli.
YiaC 和 CobB 调节大肠杆菌中的赖氨酸乳酰化
DOI:10.1038/s41467-022-34399-y
发表时间:2022-11-04
期刊:NATURE COMMUNICATIONS
影响因子:16.6
作者:Dong, Hanyang;Zhang, Jianji;Zhang, Hui;Han, Yue;Lu, Congcong;Chen, Chen;Tan, Xiaoxia;Wang, Siyu;Bai, Xue;Zhai, Guijin;Tian, Shanshan;Zhang, Tao;Cheng, Zhongyi;Li, Enmin;Xu, Liyan;Zhang, Kai
通讯作者:Zhang, Kai
DNA-guided photoactivatable probe-based chemical proteomics reveals the reader protein of mRNA methylation.
DNA 引导的基于光激活探针的化学蛋白质组学揭示了 mRNA 甲基化的读取蛋白
DOI:10.1016/j.isci.2021.103046
发表时间:2021-09-24
期刊:iScience
影响因子:5.8
作者:Huang Y;Bai X;Guo Z;Dong H;Fu Y;Zhang H;Zhai G;Tian S;Wang Y;Zhang K
通讯作者:Zhang K
Effects of lysine 2-hydroxyisobutyrylation on bacterial FabI activity and resistance to triclosan
赖氨酸2-羟基异丁酰化对细菌FabI活性和三氯生耐药性的影响
DOI:10.1016/j.biochi.2021.01.011
发表时间:2021
期刊:Biochimie
影响因子:3.9
作者:Zheng Yiqiang;Dong Hanyang;Bai Xue;Cui Hui;Li Mulin Jun;Wu Hui-Yuan;Zhang Kai
通讯作者:Zhang Kai
Systematic Proteome and Lysine Succinylome Analysis Reveals Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Carcinoma.
系统蛋白质组和赖氨酸琥珀酰组分析揭示食管鳞状细胞癌中低琥珀酰化增强细胞迁移
DOI:10.1074/mcp.ra120.002150
发表时间:2021
期刊:Molecular & cellular proteomics : MCP
影响因子:--
作者:Guo Z;Pan F;Peng L;Tian S;Jiao J;Liao L;Lu C;Zhai G;Wu Z;Dong H;Xu X;Wu J;Chen P;Bai X;Lin D;Xu L;Li E;Zhang K
通讯作者:Zhang K
TmcA functions as a lysine 2-hydroxyisobutyryltransferase to regulate transcription
TmcA 作为赖氨酸 2-羟基异丁酰转移酶来调节转录
DOI:10.1038/s41589-021-00906-3
发表时间:2021-12-13
期刊:NATURE CHEMICAL BIOLOGY
影响因子:14.8
作者:Dong, Hanyang;Zhao, Yujie;Zhang, Kai
通讯作者:Zhang, Kai
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