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

Autor:	Tristán-Ramos P; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain.; Dept. Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071, Granada, Spain., Rubio-Roldan A; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain., Peris G; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain.; Dept. of Computer Languages and Systems, Universitat Jaume I, Castellón de la Plana, 12071, Spain., Sánchez L; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain., Amador-Cubero S; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain., Viollet S; Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France., Cristofari G; Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France., Heras SR; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Av. de la Ilustración, 114, 18016, Granada, Spain. sara.rodriguez@genyo.es.; Dept. Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071, Granada, Spain. sara.rodriguez@genyo.es.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Nov 11; Vol. 11 (1), pp. 5712. Date of Electronic Publication: 2020 Nov 11.
DOI:	10.1038/s41467-020-19430-4
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu