Abstract

The advent of RNA sequencing technology has stimulated rapid advances in our understanding of the transcriptome, including discovery of the vast RNA complement generated by transcript splice variation and the expansion of our knowledge of non-coding RNAs. One non-coding RNA subtype, microRNAs (miRNAs), are particularly well studied, primarily because of their important roles as post-transcriptional gene regulators. The first miRNA was identified in the early 1990s and there are now thought to be around 1000 distinct miRNAs in man, with each cell type expressing a distinct repertoire. Increasing evidence has implicated miRNAs as having causative roles in a variety of lung diseases and has driven investigations into their potential as therapeutic targets.

Derivation and function

miRNAs are generally derived from precursor transcripts termed pri-miRNAs. These pri-miRNAs can either contain a single short miRNA hairpin of only about 100 nucleotides (nt) in length, or they can contain multiple miRNA hairpins. A number of miRNAs, known as miRtrons, are excised from the introns of protein-coding genes by the cellular splicing machinery.

The product of miRNA processing is a 19–25 nt RNA molecule that can be incorporated into a cytoplasmic protein complex called RISC, the RNA-Induced Silencing Complex. Once in the context of RISC, miRNAs target specific mRNAs through Watson–Crick base pairing which predominately involves only bases 2–8 of the miRNA, known as the ‘seed’. A single miRNA may …