New Insights into the Functions of Nucleic Acids Controlled by Cellular Microenvironments

The right-handed double-helical B-form structure (B-form duplex) has been widely recognized as the canonical structure of nucleic acids since it was first proposed by James Watson and Francis Crick in 1953. This B-form duplex model has a monochronic and static structure and codes genetic information within a sequence. Interestingly, DNA and RNA can form various non-canonical structures, such as hairpin loops, left-handed helices, triplexes, tetraplexes of G-quadruplex and i-motif, and branched junctions, in addition to the canonical structure. The formation of non-canonical structures depends not only on sequence but also on the surrounding environment. Importantly, these non-canonical structures may exhibit a wide variety of biological roles by changing their structures and stabilities in response to the surrounding environments, which undergo vast changes at specific locations and at specific times in cells. Here, we review recent progress regarding the interesting behaviors and functions of nucleic acids controlled by molecularly crowded cellular conditions. New insights gained from recent studies suggest that nucleic acids not only code genetic information in sequences but also have unknown functions regarding their structures and stabilities through drastic structural changes in cellular environments.