type of tRNA (e.g., tRNAphe) is recognized only by a cognatesynthetase enzyme (i.e., phenylalanine
tRNA synthetase), which allows only the proper amino acid to be covalently attached to the 3-terminus
(i.e., phenylalanine). There are two major classes of synthetases, with differing architectures and strategies
for tRNA recognition.^55 They are often distinguished by the fact that Class 1 synthetases aminoacylate the
2 -OH of the tRNA acceptor stem, while Class 2 synthetases aminoacylate the 3-OH. The specificity
determinants that govern tRNA–synthethase interactions is a major subject of research, as proper tRNA-
synthetase recognition is the foundation of a functional genetic code.
7.3.3 Ribosomal RNAs and the Ribosome
The longest, most highly conserved, and most abundant RNA molecules in a cell are the rRNAs. These
gigantic transcripts, together with a defined set of ribosomal proteins, assemble to form the two ribosomal
subunits (30S and 50S in bacteria; 40S and 60S in eukaryotes) that represent the functional machinery for
prokaryotic and eukaryotic ribosomes (Figure 7.27).
The overwhelming majority of ribosomal mass is represented by rRNA, which provides the scaffold for
mRNA and tRNA binding, helps translocate them through the ribosomal core, and also catalyzes peptide
bond formation. Intrinsic ribosomal proteins (designated S1, S2, etc. for proteins of the small subunit and
L1, L2, etc. for proteins of the large subunit) are particularly important in early stages of subunit assem-
bly, and they contribute subsequently to translation. Additional translation initiation factors(i.e., IF1-IF3),
elongation factors(i.e., EF-Tu and EF-G), and release factors(RF) help to facilitate the dynamic process
of protein synthesis by the ribosome. Intriguingly, many of these factors (such as EF-Tu, EF-G, and RF)
mimic the size, shape, and chemical properties of tRNA molecules, thereby providing important examples
of RNA–protein mimicry that is seen in many aspects of RNA biology (Figure 7.28).^56
The two ribosomal subunits are extremely stable and this has contributed to the recent success in obtain-
ing high-resolution crystal structures of the prokaryotic 30S and 50S RNA–protein particles (RNPs)
(Figure 7.29, see also the Front Cover). Building on earlier cryo-electron microscopy and biochemical studies
276 Chapter 7
Figure 7.27 Two similar designs for the ribosomal factory. Comparison of the prokaryotic and eukaryotic
ribosomes and their respective translation cofactors. The structures (above) were obtained by
cryo-electron microscopy
(Reprinted from Ref. 75. © (2001), with permission from Elsevier)