ABSTRACT
Lin-4 gene was studied as a key factor for the development of the nematode C. elegans. Upon cloning of lin-4 though, no cognate protein was assigned to it. Instead, it generated two RNA products, the premature and the mature lin-4 forms. Th e latter is complementary to repeats of the 3΄-untranslated region (UTR) of lin-14 through the translational repression of lin-14 (Lee et al. 1993), leading to the identifi cation of the fi rst miRNA. It was only seven years later when let-7, another small regulatory RNA in C. elegans with orthologs in other species, was discovered implying the existence of a conserved mechanism of post-transcriptional regulation (Reinhart et al. 2000). Apart from controlling development in C. elegans, miRNAs participate in almost all cellular functions, such as diff erentiation and organogenesis, growth control and programmed cell death in plants, worms, fl ies, fi sh, frogs and mammals. Systematic cloning of small RNAs from plants to humans revealed an increasing number of small RNAs, suggesting that a novel regulatory mechanism was potentially conserved during evolution (Lagos-Quintana et al. 2003; Lim et al. 2003; Lagos-Quintana et al. 2002; Lee et al. 2001; Lagos-Quintana et al. 2001). Using computational target predictions and genome-wide identifi cation of miRNA targets, over 10,000 miRNAs have been identifi ed in a wide range of species, and it is estimated that each animal miRNA regulates hundreds of diff erent mRNAs. Further, at least 60% of the human transcriptome is subject to regulation by miRNAs (Rajewsky and Socci 2004; Rajewsky 2006; Mashima et al. 2008; Persson et al. 2009). However, due to the large quantity predicted, only a few of them have been experimentally validated (Y. Wang et al. 2009). Once a sequence has been verifi ed to be a unique miRNA, it is assigned to the miRBase Registry according to existing nomenclature guidelines (Song et al. 2004; Y. Wang et al. 2009). Th e latest version of miRBase Registry (release April 2011) contains more than 1400 unique microRNAs found in the human genome. A mature miRNA is named as “miR” followed by a unique identifying number (miR-1, miR-2, etc.), whereas the precursor hairpin as “mir”. A 3-letter prefi x designates the origin of the miR (“hsa-miR-1” for Homo sapiens miR-1), though this labeling is less used in the literature. Herein, the “miRNA” term will be used in general, except for certain identifi ed ones, where the “miR-number” labeling will be used.
