RNA Quadruplexes that Regulate Gene Expression

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The DNA in living cells encodes for all genes. When a particular gene is switched on, the cell's machinery produces a transcript called RNA, and it is the RNA that directs the synthesis of proteins using the machinery of cells called ribosomes. We have identified short stretches of RNA that can form well defined, yet unusal quadruple helix folded structures called G-quadruplexes in many transcripts. We have recently found evidence to support that the formation of the quadruple helix in RNA can switch 'off' the gene by inhibiting the function of the ribosomes. This proposal aims to explore this recent finding and to also explore the possibility of generating molecules that can bind to quadruplexes in RNA and thus turn off the associated gene. This might in the longer term lead to a new class of therapeutic agents that function by selectively targeting RNA secondary structures rather than proteins.