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

Pablo Tristán-Ramos, Alejandro Rubio-Roldan, Guillermo Peris, Laura Sánchez, Suyapa Amador-Cubero, Sebastien Viollet, Gael Cristofari, Sara R. Heras

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Received Date: 26th May 20

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’s 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 found 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 uncover a new role for let-7, one of the most relevant microRNAs, which is to maintain somatic genome integrity by restricting L1 retrotransposition.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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