miRNAs in the brain

Several hundred microRNAs (miRNAs) have been cloned from a wide range of organisms across phylogeny. miRNAs are 19–23 nucleotide transcripts with characteristic 3′ hydroxyl and 5′ phosphate termini cleaved from a ∼70-nt hairpin precursor by Dicer Ribonuclease III (Hütvagner et al., 2001; Ketting et al., 2001). Many miRNAs, often with highly conserved sequences, have been mapped in the genomes of C. elegans, Drosophila, rodents and humans (Lagos-Quintana et al., 2001; Lau et al., 2001; Lee and Ambros, 2001; Lagos-Quintana et al., 2002; Mourelatos et al., 2002; Dostie et al., 2003). Based on the length, hairpin structure and conservation the total number of miRNAs in the Drosophila genome has been estimated to be 110 (Lai et al., 2003) and in the human genome to be 255 (Lim et al., 2003). Some miRNAs are organized in the genome as clusters which can be separated by intervals as short as a few nucleotides (Lagos-Quintana et al., 2001; Lau et al., 2001). Despite the high degree of conservation of miRNAs, their functions in general, and in mammals particularly, have not been well defined. The first two miRNAs discovered, lin-4 and let-7, were found in C. elegans where they control developmental timing. These short transcripts form imperfect base pairing with elements within the 3′ UTR of target mRNAs and attenuate their translation (Lee et al., 1993; Wightman et al., 1993; Olsen and Ambros, 1999; Reinhart et al., 2000; Slack et al., 2000).