Multiformity of a G/C Rich Segment at the Promoter-UTR Intersection of <i>RAP2C</i> Gene: Structural Validation by Circular Dichroism

The structural architecture of G/C-rich segments at genomic locations has been a subject of curiosity and a hot research topic for many decades. An abundance of these G/C tracts at promoter location, 5'-UTR, and other genomic locations divulge their biological significance. Topological structural transition by G/C-rich tracts opens new avenues for designing specific molecules for therapeutic purposes. Though various biochemical and biophysical techniques have been employed to date to unravel the mysteries of these G/C-rich structural species, circular dichroism (CD) plays a substantial role in uncovering the topological intricacies of G/C-rich tetraplexes. Herein, we employed extensive CD studies for the revelation of the topological structural transition of the G-rich segment (RAP2C45) as well as its C-rich counterpart (RAP2C45C) located at the intersection of the promoter-UTR site of the <i>RAP2C</i> gene. RAP2C45 adopts a parallel G-quadruplex structure in the Na⁺ and K⁺ cations. Temperature-dependent CD of C-rich sequence (RAP2C45C) forms an i-motif structure at low temperature and physiological pH, while an intramolecular C-hairpin is evident at room temperature. Both species coexist in solution. Self-associated noncanonical structures are promising therapeutic targets for the development of novel drugs. This study may add to gaining insight into designing specific molecules for promising therapeutic applications.