CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome

• Published in: EMBO reports 2016-08, Vol.17 (8), p.1131-1144
• Main Authors: Göke, Jonathan, Ng, Huck Hui
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Animals; Cancer therapies; Cellular biology; EMBO09; EMBO44; endogenous retrovirus; Endogenous Retroviruses - genetics; Gene expression; Gene Expression Regulation; Genetic Markers; Genome, Human; Genomes; Genomic Instability; Humans; lncRNA; Long Interspersed Nucleotide Elements; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - therapy; Oncogenes; Organ Specificity - genetics; regulation; Regulatory Sequences, Nucleic Acid; Retroelements; retrotransposon; Review; Reviews; RNA, Long Noncoding - genetics; transcription; Transcriptome
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201642743

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. Graphical Abstract Göke and Ng discuss roles of retrotransposons in gene expression regulation, the generation of gene isoforms and lncRNAs, in cellular identity, as markers of cell states, and how their dysregulation may contribute to the formation of and possibly therapeutic response in human cancers.