Hierarchical groove discrimination by Class I and II aminoacyl-tRNA synthetases reveals a palimpsest of the operational RNA code in the tRNA acceptor-stem bases

Nucleic Acids Research
Charles W Carter, Peter R Wills

Abstract

Class I and II aaRS recognition of opposite grooves was likely among the earliest determinants fixed in the tRNA acceptor stem bases. A new regression model identifies those determinants in bacterial tRNAs. Integral coefficients relate digital dependent to independent variables with perfect agreement between observed and calculated grooves for all twenty isoaccepting tRNAs. Recognition is mediated by the Discriminator base 73, the first base pair, and base 2 of the acceptor stem. Subsets of these coefficients also identically compute grooves recognized by smaller numbers of aaRS. Thus, the model is hierarchical, suggesting that new rules were added to pre-existing ones as new amino acids joined the coding alphabet. A thermodynamic rationale for the simplest model implies that Class-dependent aaRS secondary structures exploited differential tendencies of the acceptor stem to form the hairpin observed in Class I aaRS•tRNA complexes, enabling the earliest groove discrimination. Curiously, groove recognition also depends explicitly on the identity of base 2 in a manner consistent with the middle bases of the codon table, confirming a hidden ancestry of codon-anticodon pairing in the acceptor stem. That, and the lack of correlation ...Continue Reading

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Citations

Jan 23, 2020·Life·Christian Mayer
Sep 20, 2019·Theory in Biosciences = Theorie in Den Biowissenschaften·Gabriel S ZamudioMarco V José
Jul 30, 2020·Scientific Reports·Florian KaiserMichael Schroeder
Nov 30, 2019·Journal of Molecular Evolution·Julia A ShorePeter R Wills
Oct 11, 2020·International Journal of Molecular Sciences·Peter R Wills, Charles W Carter
Mar 7, 2021·Biomolecules·Charles W Carter, Peter R Wills
Mar 31, 2021·Annual Review of Biochemistry·Charles W Carter, Peter R Wills

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Methods Mentioned

BETA
acylation
X-ray
aminoacylation
protein folding
NMR

Software Mentioned

Mfold
JMP

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