Role of wobble base pair geometry for codon degeneracy: purine-type bases at the anticodon wobble position

Abstract

Codon degeneracy is a key feature of the genetic code, explained by Crick (J Mol Biol 19:548-555, 1966) in terms of imprecision of base pairing at the codon third position (the wobble position) of the codon-anticodon duplex. The Crick wobble rules define, but do not explain, which base pairs are allowed/disallowed at the wobble position of this duplex. This work examines whether the H-bonded configurations of solitary RNA base pairs can in themselves help decide which base pairs are allowed at the wobble position during codon-anticodon pairing. Taking the purine-type bases guanine, hypoxanthine, queuine and adenine as anticodon wobble bases, H-bonded pairing energies and optimized configurations of numerous RNA base pairs are calculated in gas and modeled aqueous phase at the B3LYP/6-31 G(d,p) level. Calculated descriptors of alignment of these solitary base pairs are able to screen between allowed and disallowed base pairs for all cases studied here, except two cases which invoke base-sugar interactions in the codon wobble nucleoside. The exclusion of adenine from the anticodon wobble position cannot be explained on the basis of pairing facility or base pair geometry. These DFT results thus account for the specificity and degeneracy of the genetic code for all cases involving guanine, hypoxanthine and queuine as anticodon wobble bases.

A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus

“…In vitro , Q-modified tRNA bound C-ending triplets more stably than U-ending triplets [31] . Structural studies report that Q-tRNA and G-tRNA have similar codon-recognition properties [42] , as might be naively expected because the ribose moiety differentiating Q from G does not involve the codon-recognizing portion of the nucleoside [43] ( Figure 2B ). Drosophila tRNA His injected into Xenopus oocytes translates NAU more than NAC when Q-modified and NAC when unmodified [44] .…”

Cross-Talk between Dnmt2-Dependent tRNA Methylation and Queuosine Modification

“…Thus, one might expect that queuosine modification does not affect the ability of the tRNA Asp to base-pair with the cognate aspartate codons. However, computational studies on the RNA bases concluded that queuine may have a slightly disfavored base pairing with cytosine as well as uracil [48]. This would suggest a weaker binding of Q than G and possibly a negative effect on codon-anticodon base pairing.…”

“…Especially the disallowance of guanosine-guanosine (G-G) pairing can involve a hydrogen bond between the N7 hydrogen of one G and the amino group of the other G [48]. This hydrogen bond is not possible with Q, since it lacks the 7-N position.…”

yaaJ, the tRNA-Specific Adenosine Deaminase, Is Dispensable in Bacillus subtilis

“…Base pairings between unmodified A34 and N(III) (where N denotes U, C, A, or G at the third position of the codon) are theoretically possible, though they are unstable or nonproductive, and sequencing analyses of tRNA gene sets from various organisms have revealed deductively that unmodified A34 can recognize all four nucleotides at the wobble position of the codon [ 11 , 13 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Pairings between A34 and R(III) (where R denotes a purine nucleotide) are particularly unstable, and they have been predicted to form only with non-canonical conformations of nucleotides.…”

“…The pairing of the ICG anticodon with the CGG codon does not occur because the I34-G(III) pairing likely causes steric hindrance, although it is possible only when it involves unusual tautomerization or geometry of nucleotides under specific conditions [ 13 , 24 , 27 , 28 , 29 ]. Thus, tRNA Arg (CCG) should be required for decoding CGG codons ( Figure 2 ), and both tRNA Arg (ICG) and tRNA Arg (CCG) have been shown indispensable for the viability of E. coli [ 33 ].…”