What RNA World? Why a Peptide/RNA Partnership Merits Renewed Experimental Attention

Abstract

We review arguments that biology emerged from a reciprocal partnership in which small ancestral oligopeptides and oligonucleotides initially both contributed rudimentary information coding and catalytic rate accelerations, and that the superior information-bearing qualities of RNA and the superior catalytic potential of proteins emerged from such complexes only with the gradual invention of the genetic code. A coherent structural basis for that scenario was articulated nearly a decade before the demonstration of catalytic RNA. Parallel hierarchical catalytic repertoires for increasingly highly conserved sequences from the two synthetase classes now increase the likelihood that they arose as translation products from opposite strands of a single gene. Sense/antisense coding affords a new bioinformatic metric for phylogenetic relationships much more distant than can be reconstructed from multiple sequence alignments of a single superfamily. Evidence for distinct coding properties in tRNA acceptor stems and anticodons, and experimental demonstration that the two synthetase family ATP binding sites can indeed be coded by opposite strands of the same gene supplement these biochemical and bioinformatic data, establishing a solid basis for key intermediates on a path from simple, stereochemically coded, reciprocally catalytic peptide/RNA complexes through the earliest peptide catalysts to contemporary aminoacyl-tRNA synthetases. That scenario documents a path to increasing complexity that obviates the need for a single polymer to act both catalytically and as an informational molecule.

tRNA acceptor stem and anticodon bases form independent codes related to protein folding

“…Enhanced specificity and catalytic proficiency presumably emerged later as aaRS assimilated anticodon recognition into cognate aaRS-tRNA pairs and gradually assumed their modern forms. The Acceptor-Stem Code Is Consistent with Preserving Structural Backbone Complementarity Between Extended β-Polypeptide and RNA Double Helices (49)(50)(51). Acceptor stem coding may have conferred a selective advantage by distinguishing smaller from larger amino acids and identifying β-branched, aliphatic, and carboxylate side-chains.…”

The tRNA A76 Hydroxyl Groups Control Partitioning of the tRNA-dependent Pre- and Post-transfer Editing Pathways in Class I tRNA Synthetase

“…The requirement for the tRNA-dependent pre-transfer editing pathway in vivo is completely unknown. Understanding of the physiological background may provide a clue as to whether this activity represents some relic from primordial times or a unique solution for IleRS proofreading (75). The experiments to address this important biological question are under way in our laboratory.…”

tRNA acceptor-stem and anticodon bases embed separate features of amino acid chemistry

“…24 Di Giulio 45,46 and Rodin & Ohno 47 have described models in which the anticodon loop arose from pre-existing, acceptor-stem RNA hairpins. The acceptor stem code may have helped mediate an early transitionfrom stereochemical coding of peptides directly by RNA to a rudimentary indirect coding mechanism 40,41,48 -paving the way for subsequent development of the universal genetic code and the interpretation of mRNAs by a ribosome.…”