Molecular insights into dynamic RNA quaternary assemblies

Quaternary assembly of proteins frequently plays essential roles in biological processes. In contrast, natural RNA oligomers have rarely been reported. The majority of observed RNA quaternary structures are symmetric homodimers, while recent studies have also revealed structures of heterodimers and symmetric homooligomers with more than two protomers. These higher-order assemblies adopt various intermolecular motifs including kissing-loops, pseudoknots, palindromic base-pairing, stacking, minor-groove interactions, and metal ion coordination that are found in RNA dimers. The dynamics in oligomerization vary across different segments of a single RNA as well as among different RNAs within the same family, which are primarily enabled by variable secondary structures, intermolecular motifs, and shape complementarity. These structural insights deepen our understanding of RNA multimerization mechanisms, paving the way for potential applications in condensate formation, RNA structure prediction, and therapeutic targeting and delivery.