III. RNA polymerase I makes the ribosomal RNAs. After their synthesis as a large precursor, the rRNAs are chemically modified, cleaved, and assembled into the two ribosomal subunits in the nucleolus—a distinct subnuclear structure that also helps to process some smaller RNA–protein complexes in the cell. Additional subnuclear structures (including Cajal bodies and interchromatin granule clusters) are sites where components involved in RNA processing are assembled, stored, and recycled. The high concentration of components in such “factories” ensures that the processes being catalyzed are rapid and efficient.
In the preceding section, we have seen that the final product of some genes is an RNA molecule itself, such as the RNAs 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 was a strong focus of attention for 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 units—the amino acids in proteins? This fascinating question stimulated great excitement. 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 was the code cracked step by step, but in the year 2000 the structure of the elaborate machinery by which cells read this code—the ribosome—was finally revealed in atomic detail.
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 4 different nucleotides in mRNA and 20 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 intermediary of mRNA, is instead 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 in consecutive 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 6–48. 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.