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RNA truncation by premature polyadenylation attenuates human mobile element activity

Abstract

Long interspersed elements (LINE-1s, also called L1s) are the only active members of the autonomous, non–long terminal repeat (LTR) retrotransposon family, which reshapes mammalian genomes in many different ways1,2,3,4,5. LINE-1 expression is low in most differentiated cells but high in some cancer cells, in testis and during embryonic development6,7,8,9,10,11,12. To minimize the negative impact on their hosts' genomes, many mobile elements strategically limit their amplification potential, particularly in somatic cells13,14,15. Here we show that the A-rich coding strand of the human LINE-1 contains multiple functional canonical and noncanonical polyadenylation (poly(A)) signals, resulting in truncation of full-length transcripts by premature polyadenylation. This attenuation lowers the rate of retrotransposition in assays using HeLa cells. It probably also increases the negative effects of LINE-1 insertions into genes16.

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Figure 1: Putative poly(A) sites in the human (LINE1.3), gorilla (LINE-1Gg-1A) and mouse (LINE-1spa) LINE-1 elements.
Figure 2: Use of the internal poly(A) sites of LINE-1 element.
Figure 3: 3′ ends of ESTs relative to common LINE-1 poly(A) signals.
Figure 4: 3′ RACE analysis of the prematurely terminated LINE-1.3 RNA species.

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References

  1. Lander, E.S. et al. Initial sequencing and analysis of the human genome. International Human Genome Sequencing Consortium. Nature 409, 860–921 (2001).

    CAS  PubMed  Google Scholar 

  2. Deininger, P.L., Moran, J.V., Batzer, M.A. & Kazazian, H.H. Jr. Mobile elements and genome evolution. Curr. Opin. Genet. Dev. 13, 1–8 (2003).

    Article  Google Scholar 

  3. Ostertag, E.M. & Kazazian, H.H. Jr. Biology of L1 retrotransposons. Annu. Rev. Genet. 35, 501–538 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Esnault, C., Maestre, J. & Heidmann, T. Human LINE retrotransposons generate processed pseudogenes. Nat. Genet. 24, 363–367 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Branciforte, D. & Martin, S.L. Developmental and cell type specificity of LINE-1 expression in mouse testis: implications for transposition. Mol. Cell Biol. 14, 2584–2592 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Trelogan, S.A. & Martin, S.L. Tightly regulated, developmentally specific expression of the first open reading frame from LINE-1 during mouse embryogenesis. Proc. Natl. Acad. Sci. USA 92, 1520–1524 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ostertag, E.M. et al. A mouse model of human L1 retrotransposition. Nat. Genet. 32, 655–660 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Bratthauer, G.L., Cardiff, R.D. & Fanning, T.G. Expression of LINE-1 retrotransposons in human breast cancer. Cancer 73, 2333–2336 (1994).

    Article  CAS  PubMed  Google Scholar 

  10. Asch, H.L. et al. Comparative expression of the LINE-1 p40 protein in human breast carcinomas and normal breast tissues. Oncol. Res. 8, 239–247 (1996).

    CAS  PubMed  Google Scholar 

  11. Skowronski, J., Fanning, T.G. & Singer, M.F. Unit-length line-1 transcripts in human teratocarcinoma cells. Mol. Cell. Biol. 8, 1385–1397 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Benihoud, K. et al. Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain. Oncogene 21, 5593–5600 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Deininger, P.L. & Batzer, M.A. Mammalian retroelements. Genome Res. 12, 1455–1465 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Lerat, E., Capy, P. & Biemont, C. Codon usage by transposable elements and their host genes in five species. J. Mol. Evol. 54, 625–637 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Siebel, C.W. & Rio, D.C. Regulated splicing of the Drosophila P transposable element third intron in vitro: somatic repression. Science 248, 1200–1208 (1990).

    Article  CAS  PubMed  Google Scholar 

  16. Medstrand, P., van de Lagemaat, L.N. & Mager, D.L. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res. 12, 1483–1495 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tabaska, J.E. & Zhang, M.Q. Detection of polyadenylation signals in human DNA sequences. Gene 231, 77–86 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Dombroski, B.A., Mathias, S.L., Nanthakumar, E., Scott, A.F. & Kazazian, H.H. Isolation of an active human transposable element. Science 254, 1805–1810 (1991).

    Article  CAS  PubMed  Google Scholar 

  20. Gilbert, N., Lutz-Prigge, S. & Moran, J.V. Genomic deletions created upon LINE-1 retrotransposition. Cell 110, 315–325 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Mulhardt, C. et al. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron 13, 1003–1015 (1994).

    Article  CAS  PubMed  Google Scholar 

  22. Naas, T.P. et al. An actively retrotransposing, novel subfamily of mouse L1 elements. EMBO J. 17, 590–597 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sheets, M.D., Ogg, S.C., & Wickens, M.P. Point mutations in AAUAAA and the poly (A) addition site: effects on the accuracy and efficiency of cleavage and polyadenylation in vitro. Nucleic Acids Res. 18, 5799–5805 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Skowronski, J. & Singer, M.F. Expression of a cytoplasmic LINE-1 transcript is regulated in a human teratocarcinoma cell line. Proc. Natl. Acad. Sci. USA 82, 6050–6054 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhao, J., Hyman, L. & Moore, C. Formation of mRNA 3′ ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis. Microbiol. Mol. Biol. Rev. 63, 405–445 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Colgan, D.F. & Manley, J.L. Mechanism and regulation of mRNA polyadenylation. Genes Dev. 11, 2755–2766 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Proudfoot, N. Poly(A) signals. Cell 64, 671–674 (1991).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank C. Schmid and M. Batzer for helpful comments and J. Moran, H. Kazazian Jr. and J. Goodier for providing LINE-1 vectors and for discussion. This work was supported by the US National Institutes of Health (P.D.) and the US Department of Defense Breast Cancer Research Program (V.P.-B.).

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Correspondence to Prescott Deininger.

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Perepelitsa-Belancio, V., Deininger, P. RNA truncation by premature polyadenylation attenuates human mobile element activity. Nat Genet 35, 363–366 (2003). https://doi.org/10.1038/ng1269

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