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

Modzelewski, AJ; Shao, W; Chen, J; Lee, A; Qi, X; Noon, M; Tjokro, K; Sales, G; Biton, A; Anand, A; Speed, TP; Xuan, Z; Wang, T; Risso, D; He, L

Author(s): Modzelewski, AJ; Shao, W; Chen, J; Lee, A; Qi, X; Noon, M; Tjokro, K; Sales, G; Biton, A; Anand, A; Speed, TP; Xuan, Z; Wang, T; Risso, D; He, L;
Details: Publication Year 2021-10-07,Volume 184,Issue #22,Page 5541-5558e22
Journal Title: Cell
Abstract: Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during preimplantation development of eight mammals. Induced retrotransposons exhibit similar preimplantation profiles across species, conferring gene regulatory activities, particularly through long terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposon promoter generates an N-terminally truncated Cdk2ap1(ΔN) that peaks in preimplantation embryos and promotes proliferation. In contrast, the canonical Cdk2ap1 peaks in mid-gestation and represses cell proliferation. This MT2B2 promoter, whose deletion abolishes Cdk2ap1(ΔN) production, reduces cell proliferation and impairs embryo implantation, is developmentally essential. Intriguingly, Cdk2ap1(ΔN) is evolutionarily conserved in sequence and function yet is driven by different promoters across mammals. The distinct preimplantation Cdk2ap1(ΔN) expression in each mammalian species correlates with the duration of its 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.
Publisher: Cell Press
Keywords: Cdk2; Cdk2ap1; cell proliferation; implantation; mammals; mouse; preimplantation embryos; promoters; retrotransposons; transposons
Research Division(s): Bioinformatics
PubMed ID: 34644528
Publisher's Version: https://doi.org/10.1016/j.cell.2021.09.021
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-12-07 12:04:12

Last Modified: 2021-12-09 10:44:47