Hakai调控RNA m6A修饰和性别决定的机理研究

批准号:
31970786
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
严冬
依托单位:
学科分类:
生殖细胞及性别决定
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
严冬
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中文摘要
性别决定是动物发育过程中最重要的决定之一,在昆虫中了解性别决定机制有着重要的实用价值。N6-甲基腺嘌呤(m6A)是mRNA上含量最丰富的化学修饰,m6A甲基转移酶复合物多个组分都在果蝇性别决定中发挥作用,它通过修饰性别决定主导基因Sxl的内含子,从而影响其选择性剪接。我们通过蛋白组学筛选到一个新的蛋白Hakai,它与多个m6A因子相互作用,其缺失影响Sxl mRNA的剪接和蛋白水平,因此Hakai极有可能是果蝇性别决定和m6A修饰通路一个新的基因。过去已知Hakai的主要功能是与E-cadherin结合并导致其降解,然而它的体内功能却不清楚。预实验显示Hakai可以控制上皮细胞的粘附以及E-cadherin的蛋白水平。本项目将深入解析Hakai在性别决定中的作用,它在m6A甲基转移酶复合物中的功能,以及它调控E-cadherin的分子机理,对发育生物学和RNA表观遗传都具有重要的意义。
英文摘要
Sex determination is one of the most important decisions during animal development. In insects, understanding the sex determination pathway has important practical value. N6-methyladenine(m6A) is the most abundant chemical modification in mRNA and multiple components of the m6A methyltransferase complex play a role in the sex determination of Drosophila. They act by modifying the introns of Sxl pre-mRNA, the master gene in the Drosophila sex determination pathway, thereby regulating its alternative splicing. By screening proteomics data, we have identified a new protein Hakai, which interacts with multiple factors of m6A pathway, and its absence affects the alternative splicing and protein levels of Sxl. Thus, Hakai is highly likely to be a novel gene in the Drosophila sex determination and the m6A modification pathway. It was known previously that the main function of Hakai is to bind to E-cadherin and cause its degradation, however its in vivo function is unclear. Our preliminary experiments show that Hakai controls the adhesion of epithelial cells and protein levels of E-cadherin. This proposal will provide an in-depth analysis of the role of Hakai in sex determination, its function in the m6A methyltransferase complex, and the molecular mechanism of its regulation of E-cadherin. These findings will make important contributions to the fields of developmental biology and RNA epigenetics.
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DOI:10.16288/j.yczz.23-051
发表时间:2023
期刊:遗传
影响因子:--
作者:宋鹏辉;马丽娟;严冬
通讯作者:严冬
DOI:https://doi.org/10.1038/s41467-021-22424-5
发表时间:2021
期刊:Nature Communications
影响因子:16.6
作者:Yanhua Wang;Lifeng Zhang;Hang Ren;Lijuan Ma;Jian Guo;Decai Mao;Zhongwen Lu;Lijun Lu;Dong Yan
通讯作者:Dong Yan
ac4C RNA修饰酶NAT10在发育中的功能和机制
- 批准号:32270868
- 项目类别:面上项目
- 资助金额:54万元
- 批准年份:2022
- 负责人:严冬
- 依托单位:
国内基金
海外基金
