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Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes

Author

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  • Jeffrey S. Han

    (The Johns Hopkins University School of Medicine)

  • Suzanne T. Szak

    (Biogen, Inc.)

  • Jef D. Boeke

    (The Johns Hopkins University School of Medicine)

Abstract

LINE-1 (L1) elements are the most abundant autonomous retrotransposons in the human genome, accounting for about 17% of human DNA. The L1 retrotransposon encodes two proteins, open reading frame (ORF)1 and the ORF2 endonuclease/reverse transcriptase. L1 RNA and ORF2 protein are difficult to detect in mammalian cells, even in the context of overexpression systems. Here we show that inserting L1 sequences on a transcript significantly decreases RNA expression and therefore protein expression. This decreased RNA concentration does not result from major effects on the transcription initiation rate or RNA stability. Rather, the poor L1 expression is primarily due to inadequate transcriptional elongation. Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a ‘molecular rheostat’ of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.

Suggested Citation

  • Jeffrey S. Han & Suzanne T. Szak & Jef D. Boeke, 2004. "Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes," Nature, Nature, vol. 429(6989), pages 268-274, May.
    • Handle: RePEc:nat:nature:v:429:y:2004:i:6989:d:10.1038_nature02536
    DOI: 10.1038/nature02536
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    Cited by:

    1. Chen-Yu Liu & Pau-Chung Chen & Pei-Chen Lien & Yi-Peng Liao, 2018. "Prenatal Perfluorooctyl Sulfonate Exposure and Alu DNA Hypomethylation in Cord Blood," IJERPH, MDPI, vol. 15(6), pages 1-10, May.
    2. Chatchawit Aporntewan & Chureerat Phokaew & Jittima Piriyapongsa & Chumpol Ngamphiw & Chupong Ittiwut & Sissades Tongsima & Apiwat Mutirangura, 2011. "Hypomethylation of Intragenic LINE-1 Represses Transcription in Cancer Cells through AGO2," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-13, March.
    3. Patricia Gerdes & Sue Mei Lim & Adam D. Ewing & Michael R. Larcombe & Dorothy Chan & Francisco J. Sanchez-Luque & Lucinda Walker & Alexander L. Carleton & Cini James & Anja S. Knaupp & Patricia E. Car, 2022. "Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Federica Rota & Anastasia Conti & Laura Campo & Chiara Favero & Laura Cantone & Valeria Motta & Elisa Polledri & Rosa Mercadante & Giorgio Dieci & Valentina Bollati & Silvia Fustinoni, 2018. "Epigenetic and Transcriptional Modifications in Repetitive Elements in Petrol Station Workers Exposed to Benzene and MTBE," IJERPH, MDPI, vol. 15(4), pages 1-14, April.

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