Update on Small RNAs

Although most genes use RNA in the form of mRNA as a coding intermediate for protein production, there are many genes whose final products are RNA. These noncoding RNAs range from the familiar transfer and ribosomal RNAs to the more recently discovered regulatory RNAs. One type of regulatory RNA was first discovered during the study of nematode larval development. Two approximately 22nucleotide (nt) RNAs (the lin-4 and let-7 RNAs) control developmental timing by binding to their respective mRNA targets and preventing productive use of these messages, perhaps by attenuating translation (Lee et al., 1993; Pasquinelli and Ruvkun, 2002). The let-7 RNA was found broadly throughout bilateral animals, including humans, suggesting that these two riboregulators were more than oddities of worm larval development (Pasquinelli et al., 2000). In 2001, it was discovered that these two RNAs are members of a large class of 21to 24-nt noncoding RNAs, called microRNAs (miRNAs), found in nematodes, fruitflies (Drosophila melanogaster), and humans (Lagos-Quintana et al., 2001; Lau et al., 2001; Lee and Ambros, 2001). Recent computational and molecular analyses indicate that humans have over 200 miRNA genes, nearly all of which are conserved in mice, and at least 80% of which are conserved in fish (Lim et al., 2003a). Although the functions of nearly all metazoan miRNAs are unknown, their abundance and evolutionary conservation, together with the analogy to the two founding nematode miRNAs, which are posttranscriptional gene regulators, suggests that an important mode of metazoan gene regulation had gone virtually undetected until just recently. miRNAs were also ripe for discovery in plants. In mid-2002, four groups reported RNAs with miRNA characteristics among the tiny RNAs present in Arabidopsis (Llave et al., 2002a; Mette et al., 2002; Park et al., 2002; Reinhart et al., 2002). One difference between plant and animal miRNAs is that the regulatory targets of plant miRNAs can be convincingly predicted simply by identifying mRNAs with nearperfect complementarity (Rhoades et al., 2002). Evolutionary conservation of the miRNA:mRNA pairing in Arabidopsis and rice (Oryza sativa), together with experimental evidence showing that miRNAs can direct the cleavage of the targeted mRNAs, supports the validity of these predictions (Llave et al., 2002a, 2002b; Park et al., 2002; Reinhart et al., 2002; Rhoades et al., 2002; Kasschau et al., 2003; Tang et al., 2003). With this ability to confidently predict regulatory targets for plant miRNAs, there is already an arguably broader understanding of the regulatory roles and biochemical actions of miRNAs in plants than in animals, despite the fact that the first plant miRNAs were reported less than a year ago.