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Dicer and R2D2

Published on October 1, 2007 Reviewed on August 21, 2015   35 min

A selection of talks on Biochemistry

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Dicer and R2D2.
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RNA interference is a highly conserved biological response to double-stranded RNA that results in the sequence-specific silencing of target gene expression. Prior to the discovery of RNAi as a post-transcriptional gene regulatory mechanisms in C. elegans, there had been reports of homologous-dependent gene silencing mediated by unknown substrates in organisms as diverse as insects, plants, and fungi. Various terms such as co-suppression or post-transcriptional gene silencing in quelling were given to the observation that transformation of plant or fungal genomes with a particular gene led to silencing of homologous genes in the genome. For example, introducing multiple copies of a pigment gene designed to increase the color intensity in the flower did not deepen flower color as expected. The flowers lost the pigmentation indicating that the transgenes themselves were not only inactive but also that the added DNA sequences somehow affected expression of the endogenous loci. The homology-dependent gene silencing mechanisms were also described in plants as an immune response to viral infection. In the late 1920s, it was noticed that the upper leaves of tobacco plants infected with ring spot virus showed resistance to the effects of the virus.
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The term RNAi was first coined in C. elegans in 1998 by Fire, Mello, and colleagues. They discovered that injection of double-stranded RNA into the worm induces the potent and specific silencing of genes highly homologous in sequence to the delivered double-stranded RNA. So, the trigger for RNAi and homology-dependent gene silencing is double-stranded RNA. The discovery of RNAi was followed by studies of its mechanisms.

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