RNA Quadruplexes that Regulate Gene Expression

活细胞中的DNA为所有基因编码。当一个特定的基因被打开时，细胞的机制就会产生一种被称为RNA的转录物，而正是RNA利用被称为核糖体的细胞机制来指导蛋白质的合成。我们已经确定了RNA的短片段，可以在许多转录本中形成明确的，但不寻常的四重螺旋折叠结构，称为g -四重结构。我们最近发现证据支持RNA中四重螺旋的形成可以通过抑制核糖体的功能来“关闭”基因。该提案旨在探索这一最新发现，并探索产生能够与RNA中的四联体结合从而关闭相关基因的分子的可能性。从长远来看，这可能会导致一种新的治疗药物的出现，这种药物通过选择性地靶向RNA二级结构而不是蛋白质来发挥作用。

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.