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Pseudogenes are junk DNA gene remnants generated by inactivating mutations or the loss of regulatory sequences, often following gene duplication or retrotransposition events. These pseudogenes have previously been considered to be molecular fossils derived from once-coding genes. In many cases, pseudogenes confer no observable selective advantage to the host organism and may be on a path towards removal from the genome. However, pseudogenes can also serve as raw material for the exaptation of novel functions, particularly in relation to the regulation of gene expression. Many pseudogenes are resurrected as noncoding RNA genes, which function in RNA-based gene regulatory circuits. As such, functional pseudogenes might simply be considered as 'genes'. Here, we discuss the role of these pseudogene-derived RNAs as regulators of gene expression in the context of human disease. In particular, we consider the manipulation of pseudogene transcripts through the use of antisense oligonucleotides, siRNAs, aptamers or classical gene therapy approaches as novel pharmacological strategies.

Original publication

DOI

10.2217/pgs.13.172

Type

Journal article

Journal

Pharmacogenomics

Publication Date

12/2013

Volume

14

Pages

2023 - 2034

Keywords

Epigenesis, Genetic, Evolution, Molecular, Gene Expression Regulation, Genome, Human, Humans, Molecular Targeted Therapy, Pseudogenes, RNA, Small Interfering, RNA, Untranslated, Transcription, Genetic