浙江农业科学 ›› 2021, Vol. 62 ›› Issue (2): 401-411.DOI: 10.16178/j.issn.0528-9017.20210251
王晓乐(
), 马荣荣, 鲁镇飞, 马炜炜*()
收稿日期:2020-12-22
出版日期:2021-02-11
发布日期:2021-02-04
通讯作者:
马炜炜
作者简介:*马炜炜(1986—),男,助理研究员,博士,主要从事杂交水稻杂种优势分子机理及分子育种研究,E-mail: jonathan_@163.com。基金资助:
Received:2020-12-22
Online:2021-02-11
Published:2021-02-04
摘要：
甲基化是最为广泛存在的真核生物RNA转录后修饰形式。N6-甲基腺苷(m6A)对真核生物基因转录后调控至关重要,近年来的研究揭示m6A通过招募m6A结合蛋白从而影响包括器官建成、肿瘤形成、节律钟调控及X染色体沉默在内的多种生物学进程。YTH蛋白是目前研究最为深入的m6A结合蛋白,本文从YTH蛋白的分类、识别m6A的分子机理及其生物学功能3个方面详尽阐述了真核生物中存在的多样化的YTH蛋白如何影响具有m6A修饰的RNA的命运,以及如何调控生物体生长发育。最后,讨论了目前YTH蛋白研究仍有待解决的问题,展望了其在药物研发、作物育种等领域中的应用价值。
中图分类号:
王晓乐, 马荣荣, 鲁镇飞, 马炜炜. m6A阅读者YTH蛋白的研究进展[J]. 浙江农业科学, 2021, 62(2): 401-411.
图1 人YTH家族的蛋白结构域
图2 YTH结构域形成疏水芳香族笼状结构以识别m6A 图示为酿酒酵母MRB1的YTH结构域部分结构,组成芳香族笼状结构的酪氨酸和色氨酸以球棍模型表示,3个氨基酸共同形成笼状疏水区域,结合m6A位点上的甲氨基团,m6A中的嘌呤环并不参与疏水互作。
图3 动物YTH蛋白对m6A修饰的分子调控机理 A—通过招募SRSF10及磷酸化的SRSF3,YTHDC1启动特定mRNA前体剪切;B—YTHDC1结合XIST上的m6A诱导X染色体沉默;C—YTHDC1通过招募未磷酸化的SRSF3促进RNA向核外转运;D—YTHDF1通过与mRNA终止密码子及3'UTR区域附近的m6A结合,并招募eIF3及其他翻译起始元件从而调控翻译过程;E—YTHDF3通过与YTHDF1互作增强YTHDF1介导的翻译起始;F—YTHDF3引导m6A修饰的转录本与YTHDF2结合,进入RNA降解途径;G—YTHDF2与m6A结合并招募CCR4/CAF/NOT复合体使m6A修饰的mRNA发生脱腺苷化并降解。
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