Abstract
After the discovery of the RNA interference (RNAi) mechanism, gene regulation by small RNA (sRNA)-Argonaute pathways was thought to lead invariably to the silencing or elimination of target sequences. A paradigm shifting concept known as RNA activation (RNAa) was first proposed in 2006 and has remained controversial ever since. First discovered in human and several other mammalian species, RNAa is a mechanism by which sRNA-Argonaute pathways impose positive regulation on gene expression in the nucleus via epigenetic processes. Several recent studies have unveiled unequivocal evidence that RNAa also operates in Caenorhabditis elegans by showing that 22G-RNAs engage Argonaute CSR-1 to maintain active expression of endogenous genes, and that the lin-4 microRNA binds to its own promoter to sustain its expression. These new findings revealed additional layers of operational complexity and functional sophistication for the sRNA-Argonaute pathways.
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