RNA quaternary structure and global symmetry

•Quaternary structure arises from the association of multiple macromolecular chains.•In contrast to proteins, few RNAs with symmetric quaternary structures are known.•Some riboswitches are now known to have intramolecular pseudoquaternary symmetry.•Pseudoquaternary structure stabilizes riboswitches and tunes their ligand-binding response. Many proteins associate into symmetric multisubunit complexes. Structural analyses suggested that, by contrast, virtually all RNAs with complex 3D structures function as asymmetric monomers. Recent crystal structures revealed that several biological RNAs exhibit global symmetry at the level of their tertiary and quaternary structures. Here we survey known examples of global RNA symmetry, including the true quaternary symmetry of the bacteriophage ϕ29 prohead RNA (pRNA) and the internal pseudosymmetry of the single-chain flavin mononucleotide (FMN), glycine, and cyclic di-AMP (c-di-AMP) riboswitches. For these RNAs, global symmetry stabilizes the RNA fold, coordinates ligand–RNA interactions, and facilitates association with symmetric binding partners.