L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism

TLDR

Long Interspersed Element 1 (L1) retrotransposons comprise about 17 % of the human genome, yet the mechanisms of their in vivo retrotransposition remain poorly understood. The study aims to investigate the timing and tissue specificity of L1 retrotransposition. This was achieved by generating transgenic mouse and rat models harboring human or mouse L1 elements driven by their native promoters. The experiments revealed that L1 RNA is abundant in germ cells and embryos, but retrotransposition events predominantly occur during embryogenesis rather than in germ cells, are not heritable, and can generate somatic mosaicism, implying a potential role for L1 in carcinogenesis and other diseases.

Abstract

Long Interspersed Element 1 (L1) is a retrotransposon that comprises approximately 17% of the human genome. Despite its abundance in mammalian genomes, relatively little is understood about L1 retrotransposition in vivo. To study the timing and tissue specificity of retrotransposition, we created transgenic mouse and rat models containing human or mouse L1 elements controlled by their endogenous promoters. Here, we demonstrate abundant L1 RNA in both germ cells and embryos. However, the integration events usually occur in embryogenesis rather than in germ cells and are not heritable. We further demonstrate L1 RNA in preimplantation embryos lacking the L1 transgene and L1 somatic retrotransposition events in blastocysts and adults lacking the transgene. Together, these data indicate that L1 RNA transcribed in male or female germ cells can be carried over through fertilization and integrate during embryogenesis, an interesting example of heritability of RNA independent of its encoding DNA. Thus, L1 creates somatic mosaicism during mammalian development, suggesting a role for L1 in carcinogenesis and other disease.