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

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 Cdk2ap1ΔN 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 Cdk2ap1ΔN production, reduces cell proliferation and impairs embryo implantation, is developmentally essential. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved in sequence and function yet is driven by different promoters across mammals. The distinct preimplantation Cdk2ap1ΔN 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.

Original languageEnglish
Pages (from-to)5541-5558.e22
JournalCell
Volume184
Issue number22
DOIs
StatePublished - Oct 28 2021

Keywords

  • Cdk2
  • Cdk2ap1
  • cell proliferation
  • implantation
  • mammals
  • mouse
  • preimplantation embryos
  • promoters
  • retrotransposons
  • transposons

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