A.6 How Translation Happens: Transfer RNA (tRNA)

It is one thing to create a table that shows how abbreviations for codons are mapped to abbreviations for amino acids, but it is quite another to actually implement the code with real molecules in the cell. How does a sequence of codons in the messenger RNA actually guide assembly of a polypeptide sequence of amino acids?

Time, then, to meet a second important variety of RNA, transfer RNA, or tRNA. Although made of the same four nucleotide bases as messenger RNA, a tRNA looks different. First, it is short, less than 100 bases long, compared with the thousands of bases found in many mRNAs. Second, instead of remaining a one-dimensional sequence, the tRNA folds itself into a shape like a three-leaf clover. It does this by Watson-Crick base pairing with itself. Short sequences in the tRNA are the complements of other short sequences elsewhere. These sets of base pairs find each other and bond, creating the folded structure.

At the end of the middle cloverleaf is a three-nucleotide RNA sequence called an anticodon, which is the complement of one of the codons in the messenger RNA. On the opposite end is an attachment point for a specific amino acid. Since there are 20 amino acids, there are at least 20 unique tRNAs.3 Each bears an anticodon specific to its amino acid.

For example, if the tRNA bears the anticodon AAA, then the corresponding codon in the incoming mRNA would be UUU. From the genetic code table, we know that UUU codes for the amino acid phenylalanine. Thus, the amino acid attached to the other end of the tRNA is phenylalanine. This pattern holds for all 20 amino acids; each has at least one tRNA to call its own, with the amino acid molecule attached to one end and the anticodon for that amino acid at the other.

Transfer RNA is the physical mechanism that maps the nucleotide alphabet of RNA to the amino acid alphabet of protein. tRNA is an actual molecular object with the anticodon at one end and the corresponding amino acid at the other. We have the genetic code we do because of the tRNAs we have. There does not appear to be any physical or chemical reason why the tRNA with anticodon AAA must have phenylalanine at the other end. It just worked out that way. We could easily imagine alternative genetic codes in which AAA codes for something else because its tRNA is connected to a different amino acid.