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Orienting Tetramolecular G‐Quadruplex Formation: The Quest for the Elusive RNA Antiparallel Quadruplex
Authors:Oscar Mendoza  Massimiliano Porrini  Gilmar F Salgado  Valérie Gabelica  Jean‐Louis Mergny
Institution:1. Université de Bordeaux, ARNA laboratory IECB, 2 rue Robert Escarpit, 33607 Pessac (France);2. INSERM, U869, IECB, 33600 Pessac (France)
Abstract:DNA and RNA G‐quadruplexes (G4) are unusual nucleic acid structures involved in a number of key biological processes. RNA G‐quadruplexes are less studied although recent evidence demonstrates that they are biologically relevant. Compared to DNA quadruplexes, RNA G4 are generally more stable and less polymorphic. Duplexes and quadruplexes may be combined to obtain pure tetrameric species. Here, we investigated whether classical antiparallel duplexes can drive the formation of antiparallel tetramolecular quadruplexes. This concept was first successfully applied to DNA G4. In contrast, RNA G4 were found to be much more unwilling to adopt the forced antiparallel orientation, highlighting that the reason RNA adopts a different structure must not be sought in the loops but in the G‐stem structure itself. RNA antiparallel G4 formation is likely to be restricted to a very small set of peculiar sequences, in which other structural features overcome the formidable intrinsic barrier preventing its formation.
Keywords:antiparallel G4  guided assembly  G‐quadruplexes  RNA  strand orientation
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