美国加州大学伯克利分校Lin He等研究人员合作发现，一个小鼠特异性逆转座子驱动一个保守的Cdk2ap1亚型，并对发育至关重要。相关论文于2021年10月12日在线发表于国际学术期刊《细胞》。
研究人员对八种哺乳动物植入前发育过程中的瞬时逆转座子诱导进行了描述。诱导的逆转座子基因在不同物种中表现出相似的植入前特征，特别是通过长末端重复（LTR）逆转录基因启动子赋予基因调控活性。小鼠特异性MT2B2逆转录子启动子产生了一个N端截断的Cdk2ap1ΔN，在植入前的胚胎中达到峰值，并促进增殖。相反，典型的Cdk2ap1在妊娠中期达到峰值并抑制细胞增殖。这个MT2B2启动子，其缺失废除了Cdk2ap1ΔN的产生，减少了细胞增殖并损害了胚胎植入，这是发育上的关键。
有趣的是，Cdk2ap1ΔN的序列和功能在进化上是保守的，但在哺乳动物中是由不同的启动子驱动。每个哺乳动物物种中不同的植入前Cdk2ap1ΔN的表达与其植入前发育的时间相关。因此，特定物种的转座子启动子可以产生进化上保守的、可供选择的蛋白亚型，赋予它们新的功能和特定物种的表达，从而管理基本的生物差异。
据介绍，逆转座子在重要的发育和病理过程中介导基因调节。
附：英文原文
Title: A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development
Author: Andrew J. Modzelewski, Wanqing Shao, Jingqi Chen, Angus Lee, Xin Qi, Mackenzie Noon, Kristy Tjokro, Gabriele Sales, Anne Biton, Aparna Anand, Terence P. Speed, Zhenyu Xuan, Ting Wang, Davide Risso, Lin He
Issue&Volume: 2021-10-12
Abstract: Retrotransposons mediate gene regulation in important developmental and pathologicalprocesses. Here, we characterized the transient retrotransposon induction during preimplantationdevelopment of eight mammals. Induced retrotransposons exhibit similar preimplantationprofiles across species, conferring gene regulatory activities, particularly throughlong terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposonpromoter generates an N-terminally truncated Cdk2ap1ΔN that peaks in preimplantation embryos and promotes proliferation. In contrast, thecanonical Cdk2ap1 peaks in mid-gestation and represses cell proliferation. This MT2B2 promoter, whosedeletion abolishes Cdk2ap1ΔN production, reduces cell proliferation and impairs embryo implantation, is developmentallyessential. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved in sequence and function yet is driven by different promotersacross mammals. The distinct preimplantation Cdk2ap1ΔN expression in each mammalian species correlates with the duration of its preimplantationdevelopment. Hence, species-specific transposon promoters can yield evolutionarilyconserved, alternative protein isoforms, bestowing them with new functions and species-specificexpression to govern essential biological divergence.
DOI: 10.1016/j.cell.2021.09.021
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01104-1