Publication: The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition
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Date
2020-11-11
Authors
Tristán-Ramos, Pablo
Rubio-Roldan, Alejandro
Peris, Guillermo
Sánchez, Laura
Amador-Cubero, Suyapa
Viollet, Sebastien
Cristofari, Gael
Heras, Sara R.
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Springer Nature
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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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MeSH Terms
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::Untranslated Regions::3' Untranslated Regions
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Endonucleases
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Recessive::Genes, Tumor Suppressor
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Repetitive Sequences, Nucleic Acid::Interspersed Repetitive Sequences::Retroelements::Long Interspersed Nucleotide Elements
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Protein Biosynthesis
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase::RNA-Directed DNA Polymerase
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured
Whole Genome Sequencing
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Endonucleases
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Recessive::Genes, Tumor Suppressor
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Repetitive Sequences, Nucleic Acid::Interspersed Repetitive Sequences::Retroelements::Long Interspersed Nucleotide Elements
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Protein Biosynthesis
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase::RNA-Directed DNA Polymerase
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured
Whole Genome Sequencing
DeCS Terms
CIE Terms
Keywords
Lung neoplasms, Carcinoma, squamous cell, Genes, tumor suppressor, MicroRNAs, Neoplasias pulmonares, Carcinoma de células escamosas, Genes Supresores de Tumor, MicroARNs
Citation
Tristán-Ramos P, Rubio-Roldan A, Peris G, Sánchez L, Amador-Cubero S, Viollet S, et al. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nat Commun. 2020 Nov 11;11(1):5712