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

Pablo Tristán-Ramos (1, 2) , Alejandro Rubio-Roldan (2) , Guillermo Peris (2, 3) , Laura Sánchez (2) , Suyapa Amador-Cubero (2) , Sebastien Viollet (4, 5) , Gael Cristofari (4, 5) , Sara R Heras (1, 2)

1 UGR - Universidad de Granada = University of Granada
2 Centre for Genomics and Oncological Reearch (GENYO)
3 Universitat Jaume I = Jaume I University
4 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
5 UniCA - Université Côte d'Azur

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.

Domaines: Biochimie, Biologie Moléculaire; Génétique; Cancer

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⟩