L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism

  1. Hiroki Kano1,
  2. Irene Godoy1,
  3. Christine Courtney1,
  4. Melissa R. Vetter1,
  5. George L. Gerton2,
  6. Eric M. Ostertag3,4,6 and
  7. Haig H. Kazazian, Jr1,4,5
  1. 1Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  2. 2Center for Research on Reproduction and Women's Health, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  3. 3Transposagen Biopharmaceuticals, Inc., Lexington, Kentucky 40507, USA

    Abstract

    Long Interspersed Element 1 (L1) is a retrotransposon that comprises ∼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.

    Keywords

    Footnotes

    • 4 Cosenior authors.

    • 5 Corresponding authors.

      E-MAIL kazazian{at}mail.med.upenn.edu; FAX (215) 573-7760.

    • 6 E-MAIL ostertag{at}transposagenbio.com; FAX (866) 607-5608.

    • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1803909.

    • Supplemental material is available at http://www.genesdev.org.

      • Received March 25, 2009.
      • Accepted April 21, 2009.
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