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ncRNAs (non-coding RNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. In the present chapter we consider two classes of ncRNA: miRNAs (microRNAs) which are post-transcriptional regulators of gene expression and lncRNAs (long ncRNAs) which mediate interactions between epigenetic remodelling complexes and chromatin. Mutation and misexpression of ncRNAs have been implicated in many disease conditions and, as such, pharmacological modulation of ncRNAs is a promising therapeutic approach. miRNA activity can be antagonized with antisense oligonucleotides which sequester or degrade mature miRNAs, and expressed miRNA sponges which compete with target transcripts for miRNA binding. Conversely, synthetic or expressed miRNA mimics can be used to treat a deficiency in miRNA expression. Similarly, conventional antisense technologies can be used to silence lncRNAs. Targeting promoter-associated RNAs with siRNAs (small interfering RNAs) results in recruitment of chromatin-modifying activities and induces transcriptional gene silencing. Alternatively, targeting natural antisense transcripts with siRNAs or antisense oligonucleotides can abrogate endogenous epigenetic silencing leading to transcriptional gene activation. The ability to modulate gene expression at the epigenetic level presents exciting new opportunities for the treatment of human disease.

Original publication

DOI

10.1042/bse0540127

Type

Journal article

Journal

Essays Biochem

Publication Date

2013

Volume

54

Pages

127 - 145

Keywords

Animals, Disease, Gene Silencing, Humans, MicroRNAs, Molecular Targeted Therapy, RNA, Untranslated, Transgenes