The Structure of tRNA
Transfer RNA molecules vary in length between 60 and 95 nucleotides, with the majority measuring about 75 nucleotides (much smaller than the normal mRNA strand). Regions of self-complementarity within tRNA creates a cloverleaf- shaped structure. The cloverleaf, being a cloverleaf, is comprised of three characteristic loops. In the figure above, the loop closest to the 5' end is called the dihydrouridine arm (D arm), because it contains dihydrouridine bases, which are unusual nucleotides common only to tRNA. The loop closest to the 3' end is called the T arm, after its sequence of thymine-pseudouridine-cytosine (pseudouridine is also an unusual base). The loop on the bottom of the cloverleaf contains the anticodon, which binds complementarily to the mRNA codon. Because anticodons bind with codons in antiparallel fashion, they are written from the 5' end to 3' end, the inverse of codons. For example, the anticodon in the figure above should be written 3'-CGU-5'. At the 3' end of the tRNA molecule, opposite the anticodon, extends a three nucleotide acceptor site that includes a free - OH group. A specific tRNA binds to a specific amino acid through its acceptor stem. The cloverleaf structure shown above is actually a two dimensional simplification of the actual tRNA structure. The cloverleaf is therefore called a secondary structure. In reality, the cloverleaf folds further into a tertiary structure, a sort of vague L-shape. At one end of the L lies the anticodon; at the other is the acceptor stem. The L-shaped structure simply amplifies the two active ends of tRNA: the anticodon and the acceptor stem.
The Wobble Hypothesis
The structure of the anticodon of tRNA helps to explain the degeneracy of the genetic code. Previously, in the SparkNote on the Genetic Code, we saw that more than one codon could specify a particular amino acid. However, now we know that tRNA acts as a go between for the codons of mRNA and amino acids. Each tRNA binds to a specific amino acid, but the anticodons of some tRNA molecules can bind to two or three different codons. The flexibility of some anticodons is the result of the fact that the 3' end of the anticodon is more spatially confined than the 5' end. As a result, the 5' end of the anticodon is free to hydrogen bond with several base groups located at the 3' position of the codon. This idea is called the wobble hypothesis and has been confirmed by X-ray studies that show that while the 3' and middle positions are held tightly in a specific orientation by stacking interactions, the 5' position is not. The 5' position is called the wobble position because it can move around to allow for its pairing with different bases. The wobble hypothesis means that if the first and second positions are the same, certain different bases in the third position will code for the same amino acid. Codons that specify for the same amino acid are called "synonyms."