Francis Crick is well known, not only for his work in elucidating the structure of DNA along with James Watson, but also for his hypothesizing about the nature of biology that he thought would be discovered in the wake of the publication of the structure.

Among these hypotheses was the notion of a ‘central dogma’ that described the flow of information from DNA, through RNA, to protein. It was clear how information could flow from DNA to RNA as these were written in the same language of nucleic acids. What was less clear was how this information could then be translated into a protein.

 In 1955 Crick proposed the idea of adaptor molecules that would be required to read the information on the nucleic acid and translate this into the language of proteins, comprised of Amino Acids (AA). “In its simplest form there would be 20 different kinds of adaptor molecules, one for each amino acid”

We now understand these adaptor molecules to be transfer RNAs (tRNAs), which bind both messenger RNA (mRNA) and AAs in a way that the AAs can engage in protein synthesis. These tRNAs bind the AAs on one end of the molecule and have three bases, called anticodons, that interact with the codons of the mRNA. This alone would be enough to prove Crick as prescient.

However, that only covers the first part of his statement. He goes on to say, “…and twenty different enzymes to join the amino acid to their adaptor.”

Twenty enzymes to build the adaptor molecules (tRNA with AA).

Yet again, Crick’s mental model was correct, we have a number of aminoacyl tRNA synthetase (aaRS) enzymes that specifically bind the tRNAs and AAs individually and then promote their conjugation. One might expect these synthetase enzymes to be, themselves, at least partially comprised of nucleic acids that can identify the tRNAs by their anticodons and then charge them with their appropriate, cognate, AAs. However, this is not always the case. Each tRNA is, instead, recognized by an identity element that is often discrete from the anticodon, but nevertheless serves to distinguish the correct tRNA that should be bound. These identity elements (aka identity determinants) are often located along the anticodon stem or the acceptor arm of the tRNAs, however they are not restricted to such (see Fig 2 from Giegé et al.)

Figure 2 from Giege et al: Cloverleaf folding of tRNA with location of known identity determinants and its three-dimensional L-shaped organisation.

Although it is conceivable that every individual tRNA would have a specific aaRS to charge it with its AA, “[w]ith some exceptions there is only one aaRS per isoacceptor tRNAfamily (the cognate set of tRNAs).”¹ However, I will not go into the specifics of this flexibility here.

Once a tRNA is recognized and bound by its associated aaRS, the appropriate adenylated AA is brought in to the synthetic site where it will become charged to the tRNA. Once charged, the AA will be shifted to a second binding pocket, the editing site, where it is again checked. Together, this is known as the double sieve model, where the first, coarse, sieve (occurring in the synthesis site) allows placement of correctly sized (or smaller) AAs, while the second sieve (occurring in the editing site), allows only AAs of the correct hydrophilicity, mischarged AAs are cleaved by deacetylase enzymes.²

References

1. Giegé, Richard & Eriani, Gilbert. (2014). Transfer RNA Recognition and Aminoacylation by Synthetases. 10.1002/9780470015902.a0000531.pub3.
2. Dino Moras, Proofreading in translation: Dynamics of the double-sieve model PNAS December 21, 2010 107 (51) 21949-21950; https://doi.org/10.1073/pnas.1016083107
3. Shuya Fukai et al. Structural Basis for Double-Sieve Discrimination of L-Valine from L-Isoleucine and L-Threonine by the Complex of tRNA^Val and Valyl-tRNA Synthetase. Open ArchiveDOI:https://doi.org/10.1016/S0092-8674(00)00182-3