From RNA to Protein
In the preceding section we have seen that the final product of some genes is an RNA molecule itself, such as those present in the snRNPs and in ribosomes. However, most genes in a cell produce mRNA molecules that serve as intermediaries on the pathway to proteins. In this section we examine how the cell converts the information carried in an mRNA molecule into a protein molecule. This feat of translation first attracted the attention of biologists in the late 1950s, when it was posed as the “coding problem”: how is the information in a linear sequence of nucleotides in RNA translated into the linear sequence of a chemically quite different set of subunits—the amino acids in proteins? This fascinating question stimulated great excitement among scientists at the time. Here was a cryptogram set up by nature that, after more than 3 billion years of evolution, could finally be solved by one of the products of evolution—human beings. And indeed, not only has the code been cracked step by step, but in the year 2000 the elaborate machinery by which cells read this code—the ribosome—was finally revealed in atomic detail.
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An mRNA Sequence Is Decoded in Sets of Three Nucleotides
Once an mRNA has been produced, by transcription and processing the information present in its nucleotide sequence is used to synthesize a protein. Transcription is simple to understand as a means of information transfer: since DNA and RNA are chemically and structurally similar, the DNA can act as a direct template for the synthesis of RNA by complementary base-pairing. As the term transcription signifies, it is as if a message written out by hand is being converted, say, into a typewritten text. The language itself and the form of the message do not change, and the symbols used are closely related.
In contrast, the conversion of the information in RNA into protein represents a translation of the information into another language that uses quite different symbols. Moreover, since there are only four different nucleotides in mRNA and twenty different types of amino acids in a protein, this translation cannot be accounted for by a direct one-to-one correspondence between a nucleotide in RNA and an amino acid in protein. The nucleotide sequence of a gene, through the medium of mRNA, is translated into the amino acid sequence of a protein by rules that are known as the genetic code. This code was deciphered in the early 1960s.
The sequence of nucleotides in the mRNA molecule is read consecutively in groups of three. RNA is a linear polymer of four different nucleotides, so there are 4 × 4 × 4 = 64 possible combinations of three nucleotides: the triplets AAA, AUA, AUG, and so on. However, only 20 different amino acids are commonly found in proteins. Either some nucleotide triplets are never used, or the code is redundant and some amino acids are specified by more than one triplet. The second possibility is, in fact, the correct one, as shown by the completely deciphered genetic code in Figure 6-50. Each group of three consecutive nucleotides in RNA is called a codon, and each codon specifies either one amino acid or a stop to the translation process.
genetic code is used universally in all present-day organisms. Although a few slight differences in the code have been found, these are chiefly in the DNA of mitochondria. Mitochondria have their own transcription and protein synthesis systems that operate quite independently from those of the rest of the cell, and it is understandable that their small genomes have been able to accommodate minor changes to the code (discussed in Chapter 14).
In principle, an RNA sequence can be translated in any one of three different reading frames, depending on where the decoding process begins (Figure 6-51). However, only one of the three possible reading frames in an mRNA encodes the required protein. We see later how a special punctuation signal at the beginning of each RNA message sets the correct reading frame at the start of protein synthesis.
tRNA Molecules Match Amino Acids to Codons in mRNA
The codons in an mRNA molecule do not directly recognize the amino acids they specify: the group of three nucleotides does not, for example, bind directly to the amino acid. Rather, the translation of mRNA into protein depends on adaptor molecules that can recognize and bind both to the codon and, at another site on their surface, to the amino acid. These adaptors consist of a set of small RNA molecules known as transfer RNAs (tRNAs), each about 80 nucleotides in length.
We saw earlier in this chapter that RNA molecules can fold up into precisely defined three-dimensional structures, and the tRNA molecules provide a striking example. Four short segments of the folded tRNA are double-helical, producing a molecule that looks like a cloverleaf when drawn schematically (Figure 6-52A). For example, a 5′-GCUC-3′ sequence in one part of a polynucleotide chain can form a relatively strong association with a 5′-GAGC-3′ sequence in another region of the same molecule. The cloverleaf undergoes further folding to form a compact L-shaped structure that is held together by additional hydrogen bonds between different regions of the molecule