The naturally occurring modifications, 5-methoxycarbonylmethyl-2-thiouridine (mcmsU34), at tRNA's wobble position-34, and 2-methylthio N 6 -threonylcarbamoyladenosine (mstA37), at position-37, 3′-adjacent to the anticodon in the loop of the hASLLys3UUU, are both chemically rich and constitute a unique combination in human tRNAs.
The plausible readings consider alternative solutions for the A and U nucleotides (and modifications) at the wobble position of the tRNA.
Vertebrate tRNAs also have specific modifications at certain positions in their structures that allow innate immune sensors to discriminate between them and bacterial tRNAs (Gehrig et al., 2012).
In particular, RNA modifications at the first (wobble) position of the tRNA anticodon participate in the precise decoding of the genetic code that is mediated by the codon anticodon interaction (Bjork, 1995; Yokoyama and Nishimura, 1995; Curran, 1998; Suzuki, 2005).
tRNAs are heavily modified and it is known that some of these modifications affect tRNA stability.
Replication pausing also occurs at tRNA genes.
In this study, we first analyzed RNA base modifications in tRNA molecules.
The corresponding uridines are located in helical regions (at least in the fully mature tRNA), thus perhaps relatively inaccessible to the enzyme, and these are isomerized to Ψ only in one tRNA species, whereas the other Ψ modifications, at least those in positions 38, 54 and 55 are located in loops and found in several tRNAs (see Additional file 1).
One constraint on the first anticodon sequences was that they must form stable anticodon-codon interactions in the absence of modified anticodon loop nucleotides, if, as suggested by Crick [ 44], there was no post-transcriptional modification of tRNA nucleotides at this early stage.
