Development of a highly optimized procedure for the discovery of RNA G-quadruplexes by combining several strategies

Competitive Microarray Screening Reveals Functional Ligands for the DHX15 RNA G-Quadruplex

“…14, 15 For example, RNA G-quadruplexes (rG4s), which contain guanine-rich tracks that fold to form the high-order structure, have been regarded as attractive RNA targets. 16 Several rG4s in 5′ untranslated regions (5′ UTR) have been targeted with small molecules (even with the FDA-approved drug Levofloxacin), resulting in translation inhibition. 17−19 In particular, rG4s with duplex/hairpin structures embedded in loops have also attracted attention for their unique structures and protein binding (e.g., sc1 RNA-FMRP RGG, HIV-1 RNA U3).…”

“…Ideal RNA targets for small molecules should meet the requirements of both ligandability and functional relevance. Like proteins, many RNAs can fold into diverse secondary and three-dimensional structures with hydrophobic pockets in many structures throughout the protein databank (PDB). − Moreover, these structures or conformations can be recognized by proteins or small molecules and regulate diverse functions such as translation, splicing, and RNA decay. − In some cases, targeting ligandable structures with small molecules can result in functional changes caused by altering the thermodynamic stability or conformation of the RNA. , For example, RNA G-quadruplexes (rG4s), which contain guanine-rich tracks that fold to form the high-order structure, have been regarded as attractive RNA targets . Several rG4s in 5′ untranslated regions (5′ UTR) have been targeted with small molecules (even with the FDA-approved drug Levofloxacin), resulting in translation inhibition. − In particular, rG4s with duplex/hairpin structures embedded in loops have also attracted attention for their unique structures and protein binding (e.g., sc1 RNA-FMRP RGG, HIV-1 RNA U3). , These intriguing RNA structures exhibit great potential for small molecule targeting.…”