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The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition

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  • Pablo Tristán-Ramos

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada
    Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja)

  • Alejandro Rubio-Roldan

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada)

  • Guillermo Peris

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada
    Universitat Jaume I)

  • Laura Sánchez

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada)

  • Suyapa Amador-Cubero

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada)

  • Sebastien Viollet

    (Université Côte d’Azur, CNRS, INSERM, IRCAN)

  • Gael Cristofari

    (Université Côte d’Azur, CNRS, INSERM, IRCAN)

  • Sara R. Heras

    (GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada
    Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja)

Abstract

Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy. Tumor suppressor microRNAs are ∼22nt RNAs that post-transcriptionally regulate oncogene expression and are frequently downregulated in cancer. Here we explore whether they also influence L1 mobilization. We show that downregulation of let-7 correlates with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein, ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition.

Suggested Citation

  • Pablo Tristán-Ramos & Alejandro Rubio-Roldan & Guillermo Peris & Laura Sánchez & Suyapa Amador-Cubero & Sebastien Viollet & Gael Cristofari & Sara R. Heras, 2020. "The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19430-4
    DOI: 10.1038/s41467-020-19430-4
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