Mutualism in Nucleic Acid/Peptide Domain Arrays: Implications for Origins of Life, Nanotechnology, and Diseas

The intricate connections between nucleic acids and proteins in the cell produces a network of spatially and temporally regulated mutualisms. These mutualisms likely preceded cellular life, and are essential to the central dogma. The ribosome, a conglomerate of proteins and ribosomal RNAs is conserved and regarded as the Darwinian threshold for cellular life. Less complex mutualisms are expected to have preceded the ribosome and supported the first cellular networks in protocells. The stabilization and propagation of nucleic acids with homogeneous 5'-3' linkages, a necessary prerequisite to the organization of a replicative system, was likely mediated by proteins or small peptides that served to protect nucleic acids from the harsh prebiotic environment. Peptide assemblies, which may have formed prebiotically upon concentration of peptides as short as two amino acids in a discrete area, are being explored as scaffolds for specific nucleic acid elongation. The use of peptide assemblies as scaffolds is also exploited in nanotechnology where the production of peptide hydrogels for tissue engineering continues. The complementarity of nucleic acids is manipulated in the construction of DNA origami, where its digital-like interactions are fine-tuned for the development of responsive systems. The diversity of DNA secondary structures and their context dependence extends these efforts. Guanine quadruplexes, which demonstrate efficient electron transfer are being explored as wires in bionanocircuitry. Combination of the scaffolding properties of peptide assemblies and the diverse complementary folding landscape of DNA, highlights the fabrication of artificial mutualisms. Extant mutualisms between DNA and RNA binding proteins and their targets in the cell, are responsible for the spatiotemporal regulation of cellular information flow. RNA is processed in membraneless organelles known as ribonucleoprotein granules (RNP). The liquid-liquid phase transitions that characterize the assembly and disassembly of RNP granules is mediated by RNA binding proteins with low complexity domains (LCD). Disruption of transient interactions between LCDs, or seeding of infectious domains by reversible LCD amyloids, is considered a contributor to altered ribostasis in protein misfolding diseases where deposition of RNA at disease lesions has not yet been explained. Here we explore these diverse mutualisms through structural characterization of a novel RNA/peptide co-assembly.