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MicroRNAs: SMALL RNAs WITH A BIG ROLE IN GENE REGULATION
Lin He and Gregory J. Hannon
MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complexgene regulatory networks.
RNA INTERFERENCE
(RNAi). A form of post-transcriptional gene silencing, in which dsRNA induces degradation of the homologous mRNA, mimicking the effect of the reduction, or loss, of gene activity.
Non-coding RNAs participate in a surprisingly diverse collection of regulatory events, ranging from copy-number control in bacteria1 to X-chromosome inactivation in mammals2.MicroRNAs (miRNAs) are a family of 2125-nucleotide small RNAs that, at least for those few that have characterized targets, negatively regulate gene expression at the post-transcriptional level35.
Members of the miRNA family were initially discovered as small temporal RNAs (stRNAs) that regulate developmental transitions in Caenorhabditis elegans6.Over the past few years, it has become clear that stRNAs were the prototypes of a large family of small RNAs, miRNAs, that now claim hundreds of members in worms, flies, plants and mammals. The functions of miRNAs are not limited to the regulation of developmentally timed events. Instead, they have diverse expression patterns and probably regulate many aspects of development and physiology3,4,79.Although the mechanisms through which miRNAs regulate their target genes are largely unknown, the finding that at least some miRNAs feed into the RNA INTERFERENCE (RNAi)
pathway has provided a starting point in our journey to understand the biological roles of miRNAs.
In this review, we revisit the history of miRNAs and summarize recent findings in miRNA biogenesis, translational repression and biological function. We conclude by highlighting the continuing genome-wide efforts to identify novel miRNAs and to predict their targets.
The discovery of miRNAs
The founding member of the miRNA family, lin-4,was identified in C. elegans through a genetic screen for defects in the temporal control of post-embryonic development10,11.In C. elegans,cell lineages have...