Intensified Cloning Efforts Have Revealed Numer

ulation of hematopoietic lineage differentiation in mammals (Chen et al., 2004), and control of leaf and flower trolled by miRNAs indicate that these examples represent a very small fraction of the total This review highlights what has been learned about MicroRNAs (miRNAs) are endogenous ‫22ف‬ nt RNAs that can play important regulatory roles in animals and miRNAs in the decade since the report of the lin-4 RNA and its regulation of lin-14. The major topics discussed plants by targeting mRNAs for cleavage or transla-tional repression. Although they escaped notice until are miRNA genomics, miRNA biogenesis, miRNA regulatory mechanisms, and the roles of miRNAs in gene regu-relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in latory pathways. multicellular organisms and likely influence the output of many protein-coding genes. Genomics: The miRNA Genes For seven years after the discovery of the lin-4 RNA, the genomics of this type of tiny regulatory RNA appeared In an investigation inspiring for both its perseverance simple: there was no evidence for lin-4-like RNAs be-and its scientific insight, Victor Ambros and colleagues, yond nematodes and no sign of any similar noncoding Rosalind Lee and Rhonda Feinbaum, discovered that RNAs within nematodes. This all changed upon the dis-lin-4, a gene known to control the timing of C. elegans covery that let-7, another gene in the C. elegans hetero-larval development, does not code for a protein but chronic pathway, encoded a second ‫22ف‬ nt regulatory instead produces a pair of small RNAs (Lee et al., 1993). RNA. The let-7 RNA acts to promote the transition from One RNA is approximately 22 nt in length, and the other late-larval to adult cell fates in the same way that the is approximately 61 nt; the longer one was predicted to lin-4 RNA acts earlier in development to promote the fold into a stem loop proposed to be the precursor of progression from the first larval stage to the second the shorter one. The Ambros and Ruvkun labs then no-(Reinhart et al., 2000; Slack et al., 2000). Furthermore, ticed that these lin-4 RNAs had antisense complemen-homologs of the let-7 gene were soon identified in the tarity to multiple sites in the 3Ј UTR of the lin-14 gene human and fly genomes, and let-7 RNA itself was de-This comple-tected in human, Drosophila, and eleven other bilateral mentarity fell in a region of the 3Ј UTR previously pro-animals …