A species-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for preimplantation development

Autor: Noon M, Andrew J. Modzelewski, Davide Risso, Gabriele Sales, Ting Wang, Qi X, Wanqing Shao, Jen Chen, Zhenyu Xuan, Lin He, Tjokro K, Anne Biton, Terence P. Speed, Angus Y. Lee
Rok vydání: 2021
Předmět:
Popis: Retrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1ΔN isoform to promote cell proliferation. Cdk2ap1ΔN functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1ΔN, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1ΔN expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.One Sentence SummaryIn mammalian preimplantation embryos, retrotransposon promoters generate conserved gene isoforms, confer species-specific expression, and perform essential developmental functions.
Databáze: OpenAIRE