MicroRNAs: SMALL RNAs WITH A BIG ROLE IN GENE REGULATION

MicroRNAs: SMALL RNAs WITH A BIG ROLE IN GENE REGULATION

JULY 2004 | VOLUME 5 | Lin He and Gregory J. Hannon
MicroRNAs (miRNAs) are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. Initially identified in *Caenorhabditis elegans* as genes required for the timed regulation of developmental events, miRNAs have since been found in almost all metazoan genomes, including worms, flies, plants, and mammals. MiRNAs have diverse expression patterns and likely regulate various developmental and physiological processes. The discovery of miRNAs has added a new dimension to our understanding of complex gene regulatory networks. RNA interference (RNAi) is a form of post-transcriptional gene silencing where double-stranded RNA (dsRNA) induces the degradation of homologous mRNA, mimicking the effect of reduced or lost gene activity. Non-coding RNAs, including miRNAs, participate in a wide range of regulatory events, from copy-number control in bacteria to X-chromosome inactivation in mammals. MiRNAs are typically 21-25 nucleotides long and are derived from larger precursors that form imperfect stem-loop structures. The mature miRNA is often derived from one arm of the precursor hairpin and is released through stepwise processing by two ribonuclease-III (RNase III) enzymes. MiRNAs bind to the 3' UTRs of their target genes with imperfect complementarity and function as translational repressors. The biogenesis of miRNAs involves two processing events: the initial cleavage of the nascent miRNA transcript (pri-miRNA) into a ~70-nucleotide precursor (pre-miRNA) by Drosha, and the subsequent cleavage of the pre-miRNA into the mature miRNA by Dicer. The mature miRNA strand from the miRNA/miRNA* duplex is selectively incorporated into the RNA-induced silencing complex (RISC) for target recognition, while the miRNA* strand is degraded. The functional characterization of miRNAs has been primarily based on genetic mutations in miRNA genes. For example, the fly miRNA Bantam was identified through a screen for genes promoting cell proliferation and suppressing apoptosis during tissue growth. MiRNAs have been shown to regulate various developmental processes, including larval developmental transitions, neuronal development, growth control, apoptosis, haematopoietic differentiation, and leaf development. Despite significant progress, the precise molecular mechanisms underlying post-transcriptional repression by miRNAs remain largely unknown. The functional characterization of miRNAs heavily relies on the identification of miRNA target genes, which can be achieved through experimental validation or bioinformatic predictions. Bioinformatic predictions have been particularly useful in plants, where certain miRNAs have nearly perfect complementarity with their targets, making it easier to identify target genes. Overall, the discovery and characterization of miRNAs have provided valuable insights into gene regulation and have highlighted the importance of these small, non-coding RNAs inMicroRNAs (miRNAs) are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. Initially identified in *Caenorhabditis elegans* as genes required for the timed regulation of developmental events, miRNAs have since been found in almost all metazoan genomes, including worms, flies, plants, and mammals. MiRNAs have diverse expression patterns and likely regulate various developmental and physiological processes. The discovery of miRNAs has added a new dimension to our understanding of complex gene regulatory networks. RNA interference (RNAi) is a form of post-transcriptional gene silencing where double-stranded RNA (dsRNA) induces the degradation of homologous mRNA, mimicking the effect of reduced or lost gene activity. Non-coding RNAs, including miRNAs, participate in a wide range of regulatory events, from copy-number control in bacteria to X-chromosome inactivation in mammals. MiRNAs are typically 21-25 nucleotides long and are derived from larger precursors that form imperfect stem-loop structures. The mature miRNA is often derived from one arm of the precursor hairpin and is released through stepwise processing by two ribonuclease-III (RNase III) enzymes. MiRNAs bind to the 3' UTRs of their target genes with imperfect complementarity and function as translational repressors. The biogenesis of miRNAs involves two processing events: the initial cleavage of the nascent miRNA transcript (pri-miRNA) into a ~70-nucleotide precursor (pre-miRNA) by Drosha, and the subsequent cleavage of the pre-miRNA into the mature miRNA by Dicer. The mature miRNA strand from the miRNA/miRNA* duplex is selectively incorporated into the RNA-induced silencing complex (RISC) for target recognition, while the miRNA* strand is degraded. The functional characterization of miRNAs has been primarily based on genetic mutations in miRNA genes. For example, the fly miRNA Bantam was identified through a screen for genes promoting cell proliferation and suppressing apoptosis during tissue growth. MiRNAs have been shown to regulate various developmental processes, including larval developmental transitions, neuronal development, growth control, apoptosis, haematopoietic differentiation, and leaf development. Despite significant progress, the precise molecular mechanisms underlying post-transcriptional repression by miRNAs remain largely unknown. The functional characterization of miRNAs heavily relies on the identification of miRNA target genes, which can be achieved through experimental validation or bioinformatic predictions. Bioinformatic predictions have been particularly useful in plants, where certain miRNAs have nearly perfect complementarity with their targets, making it easier to identify target genes. Overall, the discovery and characterization of miRNAs have provided valuable insights into gene regulation and have highlighted the importance of these small, non-coding RNAs in
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Understanding MicroRNAs%3A small RNAs with a big role in gene regulation