Читать книгу Chemistry and Biology of Non-canonical Nucleic Acids - Naoki Sugimoto - Страница 32

Bulge loop is a region in which unpaired nucleotides present on one strand of a continuous duplex. In structures of natural RNAs, the most common bulge loop contains one nucleotide. When single nucleotide bulge loop forms internal stack within the duplex, the helicity of the duplex is distorted, resulting in a kink of the helix axis (Figure 2.9). When the bulged nucleotide is looped out in solvent, the overall duplex geometries can remain close to the canonical A-form (Figure 2.9). The bulged nucleobases create unique recognition sites for proteins both directly, by acting as a molecular handle, and indirectly, by distorting the RNA backbone and allowing the proteins access to base pairs in a groove [19]. The kink of the helix caused by the bulge loop also contributes to the shaping of the overall RNA structure. Thermodynamic parameters for single nucleotide bulges indicate that the bulges destabilize the helix. The destabilization effect little depends on the identity of the bulged nucleobase [20]. On the other hand, destabilization does depend on the adjacent base pairs [20b]. As it can be expected, bulge loop with longer nucleotides more destabilizes the RNA structure [21].

Figure 2.8 Hairpin structure. (a) General secondary structure of hairpin. (b) Sequence and tertiary structure of typical RNA hairpin with stable UUCG tetraloop sequence (PDB ID: 2KOC). Top view of UUCG tetraloop sequence is shown on right side of the structure. Hydrogen bonds formed within the UUCG tetraloop are shown as dashed lines.

Figure 2.9 Bulge structure. (a) General secondary structure of bulge. (b) Sequence and tertiary structure of RNA hairpin containing single nucleotide bulges, which is derived from an RNA element responsible for dynein-mediated localization of Drosophila mRNA (PDB ID: 2KE6). Bulged nucleobases are emphasized dark. Secondary structure and side view of the region forming single nucleotide bulges are shown in right boxes surrounded by solid and dashed lines.