Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Human LINE retrotransposons generate processed pseudogenes

Nature Genetics volume 24, pages 363–367 (2000)Cite this article

Abstract

Long interspersed elements (LINEs) are endogenous mobile genetic elements1,2,3,4 that have dispersed and accumulated in the genomes of higher eukaryotes via germline transposition, with up to 100,000 copies in mammalian genomes. In humans, LINEs are the major source of insertional mutagenesis, being involved in both germinal and somatic mutant phenotypes4. Here we show that the human LINE retrotransposons, which transpose through the reverse transcription of their own transcript2, can also mobilize transcribed DNA not associated with a LINE sequence by a process involving the diversion of the LINE enzymatic machinery by the corresponding mRNA transcripts. This results in the ‘retroposition’ of the transcribed gene and the formation of new copies that disclose features characteristic of the widespread and naturally occurring processed pseudogenes: loss of intron and promoter, acquisition of a poly(A) 3′ end and presence of target-site duplications of varying length5,6. We further show–by introducing deletions within either coding sequence of the human LINE–that both ORFs are necessary for the formation of the processed pseudogenes, and that retroviral-like elements are not able to produce similar structures in the same assay. Our results strengthen the unique versatility of LINEs as genome modellers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Processed pseudogene formation and rationale of the assay.
Figure 2: LINEs induce processed pseudogene formation.
Figure 3: The two LINE ORFs are necessary for processed pseudogene formation.
Figure 4: Absence of sequence specificity for mRNA retroposition, but evidence for strong cis effects.
Figure 5: Cis and trans effects of LINEs.

Similar content being viewed by others

References

  1. Jensen, S. & Heidmann, T. An indicator gene for detection of germline retrotransposition in transgenic drosophila demonstrates RNA-mediated transposition of the LINE I element. EMBO J. 10, 1927–1937 (1991).

    Article  CAS  Google Scholar 

  2. Moran, J.V. et al. High frequency retroposition in cultured mammalian cells. Cell 87, 917–927 (1996).

    Article  CAS  Google Scholar 

  3. Boeke, J.D. & Stoye, J.P. Retrotransposons, endogenous retroviruses, and the evolution of retroelements. in Retroviruses (eds Coffin, J.M., Hughes, S.H. & Varmus, H.E.) 343– 435 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1997).

    Google Scholar 

  4. Kazazian, H.H.J. & Moran, J.V. The impact of L1 retrotransposons on the human genome. Nature Genet. 19, 19–24 (1998).

    Article  CAS  Google Scholar 

  5. Vanin, E.F. Processed pseudogenes: characteristics and evolution. Annu. Rev. Genet. 19, 253–272 ( 1985).

    Article  CAS  Google Scholar 

  6. Weiner, A.M., Deininger, P.L. & Efstratiadis, A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem. 55, 631–661 (1986).

    Article  CAS  Google Scholar 

  7. Heidmann, O. & Heidmann, T. Retrotransposition of a mouse IAP sequence tagged with an indicator gene. Cell 64, 159–170 (1991).

    Article  CAS  Google Scholar 

  8. Maestre, J., Tchénio, T., Dhellin, O. & Heidmann, T. mRNA retroposition in human cells: processed pseudogene formation. EMBO J. 14, 6333–6338 ( 1995).

    Article  CAS  Google Scholar 

  9. Dombroski, B.A., Mathias, S.L., Nanthakumar, E., Scott, A.F. & Kazazian, H.H. Isolation of an active human transposable element. Science 254, 1805– 1808 (1991).

    Article  CAS  Google Scholar 

  10. Dhellin, O., Maestre, J. & Heidmann, T. Functional differences between the human LINE retrotransposon and retroviral reverse transcriptases for in vivo mRNA reverse transcription. EMBO J. 16, 6590–6602 (1997).

    Article  CAS  Google Scholar 

  11. Kazazian, H.H.J. An estimated frequency of endogenous insertional mutations in human. Nature Genet. 22, 130 (1999).

    Article  CAS  Google Scholar 

  12. Moran, J.V., DeBerardinis, R.J. & Kazazian, H.H. Jr Exon shuffling by L1 retrotransposition. Science 283, 1530–1534 (1999).

    Article  CAS  Google Scholar 

  13. Eickbush, T. Exon shuffling in retrospect. Science 283, 1465–1467 (1999).

    Article  CAS  Google Scholar 

  14. Brosius, J. Retroposons–seeds of evolution. Science 15, 753 (1991).

    Article  Google Scholar 

  15. Lahn, B.T. & Page, D.C. Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nature Genet. 21, 429–433 ( 1999).

    Article  CAS  Google Scholar 

  16. Finnegan, D.J. The I factor and I-R hybrid dysgenesis in Drosophila melanogaster. in Mobile DNA (eds Berg, D.E. & Howe, M.M.) 503– 517 (American Society for Microbiology, Washington, DC, 1989).

    Google Scholar 

  17. Boeke, J.D. LINEs and Alu–the polyA connection. Nature Genet. 16, 6–7 (1997).

    Article  CAS  Google Scholar 

  18. Tchénio, T., Ségal-Bendirdjian, E. & Heidmann, T. Generation of processed pseudogenes in murine cells. EMBO J. 12, 1487– 1497 (1993).

    Article  Google Scholar 

  19. Klenerman, P., Hengartner, H. & Zinkernagel, R.M. Anon-retroviral RNA virus persists in DNA form. Nature 390, 298–301 ( 1997).

    Article  CAS  Google Scholar 

  20. Weiss, R.A. & Kellam, P. Illicit viral DNA. Nature 390, 235–236 ( 1997).

    Article  CAS  Google Scholar 

  21. Gabriel, A. & Teng, S.-C. LCMV cDNA formation: which reverse transcriptase is responsible? Trends Genet. 14, 220–221 (1998).

    Article  CAS  Google Scholar 

  22. Carlton, M.B., Colledge, W.H. & Evans, M.J. Generation of a pseudogene during retroviral infection. Mamm. Genome 6, 90–95 (1995).

    Article  CAS  Google Scholar 

  23. Boeke, J.D., Garfinkel, D.J., Styles, C.A. & Fink, G.R. Ty elements transpose through an RNA intermediate. Cell 40, 491–500 (1985).

    Article  CAS  Google Scholar 

  24. Dornburg, R. & Temin, H.M. cDNA genes formed after infection with retroviral vector particles lack the hallmarks of natural processed pseudogenes. Mol. Cell. Biol. 10, 68– 74 (1990).

    Article  CAS  Google Scholar 

  25. Levine, K.L. et al. Unusual features of integrated cDNAs generated by infection with genome-free retroviruses. Mol. Cell. Biol. 10, 1891–1900 (1990).

    Article  CAS  Google Scholar 

  26. Derr, L.K., Strathern, J.N. & Garfinkel, D.J. RNA-mediated recombination in S. cerevisiae. Cell 67, 355–364 (1991).

    Article  CAS  Google Scholar 

  27. Martin, S.L. Ribonucleoprotein particles with LINE-1 RNA in mouse embryonal carcinoma cells. Mol. Cell. Biol. 11, 4804– 4807 (1991).

    Article  CAS  Google Scholar 

  28. Hohjoh, H. & Singer, M. Cytolasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA. EMBO J. 15 , 630–639 (1996).

    Article  CAS  Google Scholar 

  29. Sandmeyer, S. Targeting transposition: at home in the genome. Genome Res. 8, 416–418 (1998).

    Article  CAS  Google Scholar 

  30. Kim, J.M., Vanguri, S., Boeke, J.D., Gabriel, A. & Voytas, D.F. Transposable element and genome organisation: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence. Genome Res. 8, 464 –478 (1998).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Kazazian for the LINE pL1.2A plasmid; F. Dautry for the CMV-β-globin plasmid; O. Dhellin for constant help and advice; L. Bénit for help with computer searches; and C. Lavialle for comments and critical reading of the manuscript. This work was supported by the CNRS and a grant from the ARC to T.H.

Author information

Authors and Affiliations

  1. Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs , Institut Gustave Roussy, CNRS UMR 1573, Villejuif Cedex, France

    Cécile Esnault, Joël Maestre & Thierry Heidmann

Authors
  1. Cécile Esnault
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joël Maestre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thierry Heidmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thierry Heidmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esnault, C., Maestre, J. & Heidmann, T. Human LINE retrotransposons generate processed pseudogenes. Nat Genet 24, 363–367 (2000). https://doi.org/10.1038/74184

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/74184

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing