南湖新闻网讯 近日,华中农业大学水产学院鱼类发育与遗传育种团队梅洁教授课题组和武汉大学肖锐课题组合作研究成果发表,研究揭示了m6A读取器Igf2bp3通过调节m6A修饰生殖质基因的表达以实现斑马鱼生殖质组装的分子机制。
生殖质是具有特定形态结构的细胞质,包含卵母细胞遗传的各种RNA和蛋白质复合物,对生殖发育起到至关重要的作用。生殖质组装是将生殖质RNA和蛋白招募到指定位置并进行组装的动态过程,决定了未来生殖细胞的命运。大量研究表明在斑马鱼早期胚胎发育过程中,Bucky ball (Buc)通过调控生殖质mRNA表达在生殖质组装过程中发挥重要功能,但其RNA调控机制还不清楚。
研究发现m6A读取器Igf2bp3与Buc相互作用,并与之共定位于生殖质中。与buc突变体表型相似,igf2bp3母源突变导致异常的生殖质组装和生殖细胞分化缺陷,该表型可通过注射igf2bp3 mRNA进行部分挽救。进一步研究发现,Igf2bp3作为m6A识别蛋白通过结合m6A修饰的生殖质相关mRNA来抑制其降解。
该研究揭示了Igf2bp3作为Buc的直接效应蛋白,介导m6A修饰依赖的生殖质相关mRNA的基因表达调控,并维持正常的生殖质组装(图1)。该工作阐述了m6A修饰在鱼类生殖质组装过程中的作用,为鱼类生殖发育研究提供了参考。
【英文摘要】
Bucky ball (Buc) is involved in germ plasm (GP) assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism. The present study demonstrates that an m6A reader Igf2bp3 interacts and colocalizes with Buc in the GP. Similar to the loss of Buc, the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification, which can be partially restored by the injection of igf2bp3 mRNA. Igf2bp3 binds to m6A-modified GP-organizer and GP mRNAs in an m6A-dependent manner and prevents their degradation. These findings indicate that the functions of Igf2bp3, a direct effector protein of Buc, in GP mRNA expression and GP assembly involve m6A-dependent regulation; these results emphasize a critical role of m6A modification in the process of GP assembly.
论文链接:https://www.sciencedirect.com/science/article/pii/S209592732100116X