In The Genetic Code, we explained how each
codon in messenger RNA (mRNA) codes for a
specific amino acid, and that in the process of translation the mRNA brings the
amino acids together to form proteins. That explanation is correct, but it is
also simplified, and overlooks a crucial component of the translation process.
That component is transfer RNA (tRNA), which acts as a kind of link between
the information encoded in the mRNA and the amino acids. If the mRNA is a code,
then the tRNA is the key that interprets that code into physical proteins.
This section will describe the structure of tRNA and describe how tRNA can
"carry" amino acids; knowledge of these aspects of tRNA will be vital for
understanding the actual process of proteins synthesis covered next
section.
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.
Figure %: tRNA Cloverleaf 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.
