title: CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome.
abstract: The human genome contains millions of fragments from retrotransposons-highly repetitive DNA sequences that were once able to "copy and paste" themselves to other regions in the genome. However, the majority of retrotransposons have lost this capacity through acquisition of mutations or through endogenous silencing mechanisms. Without this imminent threat of transposition, retrotransposons have the potential to act as a major source of genomic innovation. Indeed, large numbers of retrotransposons have been found to be active in specific contexts: as gene regulatory elements and promoters for protein-coding genes or long noncoding RNAs, among others. In this review, we summarise recent findings about retrotransposons, with implications in gene expression regulation, the expansion of gene isoform diversity and the generation of long noncoding RNAs. We highlight key examples that demonstrate their role in cellular identity and their versatility as markers of cell states, and we discuss how their dysregulation may contribute to the formation of and possibly therapeutic response in human cancers.
authors.affiliation: Computational and Systems Biology, Genome Institute of Singapore, Singapore gokej@gis.a-star.edu.sg.
authors.forename: Jonathan
authors.identifier: 0000-0002-0825-4991
authors.initials: J
authors.lastname: Göke
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, Singapore Department of Biochemistry, National University of Singapore, Singapore Department of Biological Sciences, National University of Singapore, Singapore School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Huck Hui
authors.initials: HH
authors.lastname: Ng
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D020077:Endogenous Retroviruses / Q000235:genetics; D005786:Gene Expression Regulation; D005819:Genetic Markers; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D009857:Oncogenes; D009928:Organ Specificity / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D018626:Retroelements; D059467:Transcriptome
chemical_list: D005819:Genetic Markers; D062085:RNA, Long Noncoding; D018626:Retroelements
keywords: endogenous retrovirus; lncRNA; regulation; retrotransposon; transcription