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

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.
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https://www.hal.inserm.fr/inserm-03261333
Contributor : Gael Cristofari Connect in order to contact the contributor
Submitted on : Tuesday, June 15, 2021 - 4:04:58 PM
Last modification on : Tuesday, July 13, 2021 - 12:40:02 PM
Long-term archiving on: : Thursday, September 16, 2021 - 6:57:03 PM

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s41467-020-19430-4.pdf
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Pablo Tristán-Ramos, Alejandro Rubio-Roldan, Guillermo Peris, Laura Sánchez, Suyapa Amador-Cubero, et al.. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.5712. ⟨10.1038/s41467-020-19430-4⟩. ⟨inserm-03261333⟩

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