Article (Scientific journals)
MiR-128 represses L1 retrotransposition by binding directly to L1 RNA
Hamdorf, Matthias; Idica, A.; Zisoulis, D. G. et al.
2015In Nature Structural and Molecular Biology, 22 (10), p. 824-831
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Keywords :
DNA methyltransferase 3B; RNA; MIRN128 microRNA, human; Article; DNA integration; DNA methylation; HeLa cell line; RNA binding; CFU counting; Cellular Reprogramming; Colony-Forming Units Assay; DNA Primers; Fibroblasts; Fluorescent Antibody Technique; Genomic Instability; HeLa Cells; Humans; Immunoblotting; Induced Pluripotent Stem Cells; Long Interspersed Nucleotide Elements; Luciferases; MicroRNAs; Mutagenesis, Insertional; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction
Abstract :
[en] Long interspersed element 1 (LINE-1 or L1) retrotransposons compose 17% of the human genome. Active L1 elements are capable of replicative transposition (mobilization) and can act as drivers of genetic diversity. However, this mobilization is mutagenic and may be detrimental to the host, and therefore it is under strict control. Somatic cells usually silence L1 activity by DNA methylation of the L1 promoter. In hypomethylated cells, such as cancer cells and induced pluripotent stem cells (iPSCs), a window of opportunity for L1 reactivation emerges, and with it comes an increased risk of genomic instability and tumorigenesis. Here we show that miR-128 represses new retrotransposition events in human cancer cells and iPSCs by binding directly to L1 RNA. Thus, we have identified and characterized a new function of microRNAs: mediating genomic stability by suppressing the mobility of endogenous retrotransposons. © 2015 Nature America, Inc. All rights reserved.
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
eid=2-s2.0-84943457469
Author, co-author :
Hamdorf, Matthias ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Idica, A.;  Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, CA, United States
Zisoulis, D. G.;  Regulus Therapeutics, San Diego, CA, United States
Gamelin, L.;  Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, CA, United States
Martin, C.;  Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, CA, United States
Sanders, K. J.;  Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, CA, United States
Pedersen, I. M.;  Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, CA, United States
External co-authors :
yes
Language :
English
Title :
MiR-128 represses L1 retrotransposition by binding directly to L1 RNA
Publication date :
2015
Journal title :
Nature Structural and Molecular Biology
ISSN :
1545-9993
Publisher :
Nature Publishing Group
Volume :
22
Issue :
10
Pages :
824-831
Peer reviewed :
Peer reviewed
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