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

Abstract

The universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyltRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported that digital correlation techniques could identify patterns in tRNA identity elements that govern recognition by synthetases. Our analysis, and the functionality of truncated synthetases that cannot recognize the tRNA anticodon, support the conclusion that the tRNA acceptor stem houses an independent code for the same 20 amino acids that likely functioned earlier in the emergence of genetics. The acceptor-stem code, related to amino acid size, is distinct from a code in the anticodon that is related to amino acid polarity. Details of the acceptor-stem code suggest that it was useful in preserving key properties of stereochemically-encoded peptides that had developed the capacity to interact catalytically with RNA. The quantitative embedding of the chemical properties of amino acids into tRNA bases has implications for the origins of molecular biology.

Coding of Class I and II Aminoacyl-tRNA Synthetases

“…1B). Direct support for the hypothesis, discussed at length in this review, is made more relevant by related work on the origin of translation [5,49–54] and the genetic code [40,41,55]. …”

“…It can be argued that the effort is fruitless as one cannot run the tape in reverse, that important and relevant witnesses are all extinct, and in particular that there is no way to test hypotheses. Our work [64,40,65,41,55,26,42,32,34,27,7,28,33,29,8,30,36,31,48], and that of others [25,66,52–54,67], tends to rebut this objection. In reality, molecular phylogenies of the Class I and II aaRS have proven to be a rich source of unexpected insights into how translation became possible and robust tools now enable us to investigate, and even recapitulate key events from the past history of life.…”

“…That two distinct protein superfamilies emerged to couple amino acid activation to ATP hydrolysis represented a conundrum that remained unanswered until a quite recent investigation connecting coding properties of tRNA bases with the physical chemistry of amino acid side-chain phase transfer and protein folding equilibria [40,41,55] provided the first clues to a possible answer (see Fig. 2).…”

“…Complementary studies of the modular aaRS architectures of both synthetase classes [23,27] led to the discovery of how the organization of tRNA coding elements record how amino acids behave in water and in protein folding [40,41]. …”

“…Those folded conformations subsequently execute the symbolic rules in the genetic coding table to make themselves and all other proteins (Fig. 2; [40]).…”