The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2020

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

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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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Origin : Publication funded by an institution

Dates and versions

inserm-03261333 , version 1 (15-06-2021)

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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, 2020, 11 (1), pp.5712. ⟨10.1038/s41467-020-19430-4⟩. ⟨inserm-03261333⟩
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