Discovery
MicroRNA (miRNA) is a class of short non-coding RNA that regulates gene expression in many eukaryotes. MicroRNA was first discovered in Caenorhabditis elegans by Victor Ambros' laboratory in 1993 (Lee et al., 1993). At the same time Gary Ruvkun's laboratory identified the first microRNA target gene (Wightman et al., 1993). Together, these two seminal discoveries identified a novel mechanism of post-transcriptional gene regulation. The history of these events has been reported recently, as remembered by the main researchers involved (Lee et al., 2004; Ruvkun et al., 2004). The realization of the importance of the discovery of microRNA, however, took about seven years and was preceded by the identification of a second microRNA in C. elegans by the Ruvkun and Horvitz laboratories and also by the rise in interest in another class of short RNA, siRNA, involved in the process of RNAi and related phenomena in plants and animals (Hamilton and Baulcombe, 1999; Zamore et al., 2000). Although the discovery of microRNA was unexpected, theoretical work on the mechanism of the lac repressor by Jacob and Monod had postulated a microRNA-like mechanism forty years earlier, see Figure 1.1 (Jacob and Monod, 1961).
Biogenesis and mechanism of action
From studies in C. elegans, Drosophila melanogaster and mammalian cell culture a model for microRNA biogenesis in animals is emerging (see Figure 1.2a and Figure 1.2b): microRNAs are transcribed by RNA polymerase II as long RNA precursors (pri-miRNAs) (Kim, 2005), which are processed in the nucleus by the RNase III enzyme Drosha and DGCR8/Pasha, to form the approximately 70 base pre-miRNA (Lee et al., 2003; Denli et al., 2004; Gregory et al., 2004; Han et al., 2004; Landthaler et al., 2004).