RNA molecules that possess catalytic activity are known as ribozymes. We saw earlier in this chapter that some ribozymes function in self-splicing reactions. In the final section of this chapter, we consider what the ability of RNA molecules to function as catalysts might mean for the early evolution of living cells. For now, we merely note that there is good reason to suspect that RNA rather than protein molecules served as the first catalysts for living cells. If so, the ribosome, with its RNA core, may be a relic of an earlier time in life’s history—when protein synthesis evolved in cells that were run almost entirely by ribozymes.
Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
The initiation and termination of translation share features of the translation elongation cycle described above. The site at which protein synthesis begins on the mRNA is especially crucial, since it sets the reading frame for the whole length of the message. An error of one nucleotide either way at this stage would cause every subsequent codon in the message to be misread, resulting in a nonfunctional protein with a garbled sequence of amino acids. The initiation step is also important because for most genes it is the last point at which the cell can decide whether the mRNA is to be translated to produce a protein. The rate of this step is thus one determinant of the rate at which any particular protein will be synthesized. We shall see in Chapter 7 how regulation of this step occurs.
The translation of an mRNA begins with the codon AUG, and a special tRNA is required to start translation. This initiator tRNA always carries the amino acid methionine (in bacteria, a modified form of methionine—formylmethionine—is used), with the result that all newly made proteins have methionine as the first amino acid at their N-terminus, the end of a protein that is synthesized first. (This methionine is usually removed later by a specific protease.) The initiator tRNA is specially recognized by initiation factors because it has a nucleotide sequence distinct from that of the tRNA that normally carries methionine.
In eukaryotes, the initiator tRNA–methionine complex (Met–tRNAi) is first loaded into the small ribosomal subunit along with additional proteins called eukaryotic initiation factors, or eIFs. Of all the aminoacyl-tRNAs in the cell, only the methionine-charged initiator tRNA is capable of tightly binding the small ribosome subunit without the complete ribosome being present, and unlike other tRNAs it binds directly to the P site (Figure 6–70). Next, the small ribosomal subunit binds to the 5ʹ end of an mRNA molecule, which is recognized by virtue of its 5ʹ cap that has previously bound two initiation factors, eIF4E and eIF4G (see Figure 6–38). The small ribosomal subunit then moves forward (5ʹ to 3ʹ) along the mRNA, searching for the first AUG; additional initiation factors that act as ATP-powered
Figure 6–68 location of the protein components of the bacterial large ribosomal subunit. The rRNAs (5S and 23S) are shown in blue and the proteins of the large subunit in green. This view is toward the outside of the ribosome; the interface with the small subunit is on the opposite face. (PDB code: 1FFK.)
Figure 6–69 Structure of the l15 protein in the large subunit of the bacterial ribosome. The globular domain of the protein lies on the surface of the ribosome and an extended region penetrates deeply into the RNA core of the ribosome. The  L15 protein is shown in green and a portion of the ribosomal RNA core is shown in blue. (From D. Klein, P.B. Moore and
T.A. Steitz, J. Mol. Biol. 340:141–177, 2004. With permission from Academic Press. PDB code: 1S72.)