Protein–Nucleic Acid Interactions 417
10.9.1 Single-Stranded RNA Recognition
Here, we describe only a few, representative RNA/protein complexes that illustrate how recognition of
single-stranded RNA occurs.
Genes in the tryptophan biosynthetic pathway in E. coliare tightly controlled in response to cellular
concentrations of the amino acid Trp, and the dimeric protein known as the trp repressor modulates tran-
scription rates of the trp operon. In many species of bacteria, the expression of these genes is also controlled
post-transcriptionally through the binding of the messenger RNA by the trp RNA-binding attenuation
protein.^59 This protein forms a molecular ring with 11 subunits. Each subunit binds the triplet GAG on the
periphery of the ring (Figure 10.21a). The RNA is recognized by its unstacked bases, which are inter-
digitated with aliphatic and aromatic amino acid side chains.
An analogous mode of recognition is used by proteins that contain an RNP-binding motif, also known
as an RNA recognition motif(RRM), which is found widely in all life forms. An example is the U1A spliceo-
some protein from the RNA-splicing machinery, which binds part of the of U1 snRNA (Figure 10.3a). A
related mode of recognition of an RNA hairpin is seen in the structure of the MS2 bacteriophage capsid
bound to the initiation site of assembly.^60
Other components of the RNA spliceosome are the Sm proteins. In eukaryotes, the Sm proteins form
heteroheptameric rings that are the main components of the spliceosomal small nuclear ribonucleoproteins
(snRNPs).^61 Surprisingly, bacteria and archaea also contain an Sm-like protein that forms a hexamer and
may serve as a carrier of small regulatory RNA and other RNA molecules (Figure 10.21b).62–65Thus, the
Sm fold represents a common modular binding unit for oligomeric RNA-binding proteins.
The S1 and KH folds are other classes of small RNA-binding motifs that occur widely in nature. The S1
domain was originally identified in the ribosomal protein S1, and it belongs to the wider OB fold such as
in the Pot protein mentioned earlier (Figure 10.8a). This motif occurs in the principal ribonucleases of mes-
senger RNA decay in E. coli. In these enzymes, the conserved ligand-binding cleft has a groove of posi-
tive charge that contains exposed aromatic residues.^66 The K homology (KH) domain, first identified in the
hnRNP K protein, is found in all taxonomic domains of life and often has a role in sequence-specific bind-
ing of RNA. They often are found as tandem copies that may be linked flexibly.^67
10.9.2 Duplex RNA Recognition
The modular zinc-finger motif plays an important role in DNA recognition (Section 10.3.3), but it has also
a second function in the cell in the recognition of RNA. For example, transcription factor TFIIIA contains
nine zinc fingers, three of which can interact with a segment of the ribosomal 5S RNA (Figure 10.22). The
fold of the 5S RNA involves both duplex regions and two loops. The helices are oriented so that the posi-
tive end of the helix dipole points towards the phosphate backbone, in a similar way to that seen in the
histone–DNA complex in the nucleosome (Figure 10.15).
A completely different mode of recognition of duplex RNA is used by the p19 protein from tombavirus
(a plant virus), which has no apparent sequence-specificity, but is specific for an optimal length of duplex
RNA. Here, a -sheet serves as a platform for interactions with the RNA, which are mostly with the phosphate
backbone and sugar 2-hydroxyl groups.^68 The p19 protein suppresses the plant’s anti-viral defence by
sequestering 19–20 long duplex RNAs that guide destruction of the viral mRNA by cellular ribonucleases.
10.9.3 Transfer RNA Synthetases
To achieve high fidelity in the translation of genetic information, the cell must ensure that each and every
tRNA is charged correctly with its corresponding amino acid. This essential task is carried out by the
aminoacyl-transfer RNA synthetases(Section 7.3.2). All synthetases catalyse a two-step process. The
first step involves the binding of the substrates – ATP and amino acid by the tRNA synthetase and the for-
mation of a covalent link between them. In the second step, the amino acid is transferred onto the tRNA.