The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition Rubio Roldan, Alejandro Peris, Guillermo Sánchez, Laura Tristán Ramos, Pablo Amador Cubero, Suyapa Rodríguez Heras, Sara 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. 2021-01-25T12:41:26Z 2021-01-25T12:41:26Z 2020-11-11 journal article Tristán-Ramos, P., Rubio-Roldan, A., Peris, G., Sánchez, L., Amador-Cubero, S., Viollet, S., ... & Heras, S. R. (2020). The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nature communications, 11(1), 1-14. [doi:10.1038/s41467-020-19430-4] http://hdl.handle.net/10481/65989 10.1038/s41467-020-19430-4 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Nature Research