RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code

Abstract

By combining crystallographic and NMR structural data for RNA-bound amino acids within riboswitches, aptamers, and RNPs, chemical principles governing specific RNA interaction with amino acids can be deduced. Such principles, which we summarize in a ''polar profile'', are useful in explaining newly selected specific RNA binding sites for free amino acids bearing varied side chains charged, neutral polar, aliphatic, and aromatic. Such amino acid sites can be queried for parallels to the genetic code. Using recent sequences for 337 independent binding sites directed to 8 amino acids and containing 18,551 nucleotides in all, we show a highly robust connection between amino acids and cognate coding triplets within their RNA binding sites. The apparent probability (P) that cognate triplets around these sites are unrelated to binding sites is %5.3 9 10 -45 for codons overall, and P % 2.1 9 10 -46 for cognate anticodons. Therefore, some triplets are unequivocally localized near their present amino acids. Accordingly, there was likely a stereochemical era during evolution of the genetic code, relying on chemical interactions between amino acids and the tertiary structures of RNA binding sites. Use of cognate coding triplets in RNA binding sites is nevertheless sparse, with only 21% of possible triplets appearing. Reasoning from such broad recurrent trends in our results, a majority (approximately 75%) of modern amino acids entered the code in this stereochemical era; nevertheless, a minority (approximately 21%) of modern codons and anticodons were assigned via RNA binding sites.A Direct RNA Template scheme embodying a credible early history for coded peptide synthesis is readily constructed based on these observations.

Imprints of the genetic code in the ribosome

“…Empirical data, although limited in the past, has yielded landmark insights. The spark-tube experiments confirmed that amino acids could have been produced abiotically in the atmosphere of the early earth (27,35), and in vitro RNA aptamer selections provided solid evidence for the association of coding triplets with cognate amino acids (28). Our usage of ribosome structural data further demonstrates the usefulness of expanding the theoretical inputs to a biological context.…”

“…We found that anticodons are selectively enriched near their respective amino acids in ribosome structures and that such enrichment is correlated with the canonical genetic code. Previously, codons and anticodons have been found enriched in the binding sites in RNA aptamers selected to bind amino acids (4,28), and conserved arginine codons have been identified to bind Arg specifically in group I self-splicing introns (11). Such experiments have provided precious, hard to obtain empirical data, demonstrating the association of coding triplets with amino acids.…”

“…In the in vitro experiments of selecting RNA aptamers to bind amino acids, both codons and anticodons are found significantly enriched in the cognate amino acid binding sites. Specifically, Arg and Ile are found to associate with both codon and anticodons, whereas His, Phe, Trp, and Tyr are associated with anticodons only (28). Interpreting the stereochemical complementarity for amino acids enriched with both codons and anticodons in RNA aptamers is difficult.…”

Perspectives in Glycomics and Lectin Engineering

“…Research on a selection of particular RNA sequences with an amino acid binding activity, and a relation of those activities to the genetic code, have revealed an evidence that there is a highly robust connection between the genetic code and RNA-amino acid binding affinity (106). It seems that the main part of the genetic code is influenced by a stereochemical prebiotic selection during the first polymerisation of G, A, V and D amino acids and g, c, u and a nucleic acids, however, only first two nucleotides of codons (n 1 n 2 ) are directly related to amino acid stereoselectivity (107).…”

The Origin of the Genetic Code: Matter of Metabolism or Physicochemical Determinism?

“…Indeed, the physicochemical theory of the origin of the genetic code suggests that these properties have been the main selective pressure that determined the organisation of the genetic code (Sonneborn 1965;Woese et al 1966;Fitch and Upper 1987;Di Giulio 1997). A prediction in part equivalent is also made by the stereochemical theory of the origin of the genetic code that maintains that interactions between codons or anticodons and amino acids have been the main forces that organised the genetic code (Woese 1967;Shimizu 1982;Szathmáry 1993;Yarus 1998;Yarus et al 2009). Therefore, also for the stereochemical hypothesis the physicochemical properties of amino acids were essential in organising the code.…”