FIGURE 1.

Left-handed Z-conformations can be found within a variety of RNA functional sites. (A) Double-stranded Z-RNA (middle) is best described as being composed of dinucleotide building blocks, where the nucleobase alternates between the anti- and syn-conformations, along with alternating ribose sugar puckers (C2′-endo/C3′-endo conformations). The weak but characteristic lone pair–π contact is shown as a red triangle. The particular Z-geometry with sugar pointing in opposite directions is found in other structural contexts, such as, for example, the ligand binding site of the purine riboswitch (PDB: 4FE5, Batey et al. 2004), and the core of the pUG G-quadruplex (PDB: 7MKT, Roschdi et al. 2022). (B) Potential mechanisms for Z-RNA formation and stabilization in vivo. First, Zα binds nonspecifically to A-RNA near a Z-prone region. From here, Zα may allosterically push the Z-prone region into the Z-conformation or may have to stabilize transiently sampled Z-conformations. Each of these mechanisms may involve one or more intermediate steps.