Ribosomal RNA
A Liljas, Lund University, Lund, Sweden
© 2013 Elsevier Inc. All rights reserved.
Glossary
Anticodon Three nucleotides of a loop of tRNA that forms
base pairs with the codon of the mRNA.
CCA-end The 3′ end of the tRNA to which the amino acids
are attached.
Codon A base triplet of the mRNA that corresponds to an
amino acid in a growing polypeptide.
EF-G Elongation factor G, which translocates the
peptidyl-tRNA from the A- to the P-site.
EF-Tu Elongation factor Tu, which carries the aminoacyl
tRNA into the ribosome.
mRNA Messenger RNA, the genetic message according to
which proteins are synthesized on the ribosome.
rRNA Molecules
The small ribosomal subunit is composed of one ribosomal
RNA (rRNA) molecule. In bacteria (Escherichia coli will be used
as the reference organism in this article), it is called the 16S
RNA based upon its sedimentation velocity. In E. coli, the 16S
RNA has 1542 nucleotides. In other organisms, the size of the
corresponding RNA molecule varies. In the large ribosomal
subunit, there is usually one small RNA molecule called the
5S RNA composed of 120 nucleotides. The large RNA molecule
in bacteria is called the 23S RNA. In E. coli, the 23S RNA has
2904 nucleotides, but its size also varies between different
species and is sometimes found as several pieces.
The rRNAs have been used for studies of evolution. Since all
organisms have ribosomes that have evolved from a common
ancestor, the nucleotide sequences of rRNA have been used to
identify the relationship between species. In this way, Woese
and Fox showed that Archaea are not a subgroup of bacteria but
form their own kingdom.
Structure of rRNA
The structure of the rRNAs has been studied by a variety of
methods since the first sequences became available. From
sequence information, it is possible to analyze the potential
for base pairing. Sequences from numerous species provided
conserved secondary structures as well as the species variation.
The secondary structures of the rRNAs have been established
and confirmed with chemical methods and subsequently with
crystallographic structures. In E. coli, the 16S RNA is composed
of 45 double-stranded helices (H1-H45) and the 23S RNA of
101 helices (H1-H101). The 23S rRNA molecule of the large
subunit forms six domains (Figure 1(a)), whereas the 16S
rRNA of the small subunit is organized into four domains
(Figure 1(b)).
244 Brenner’s Encyclopedia of Genetics, 2nd edition, Volume 6
Peptidyl transfer The transfer of the peptide from the tRNA
in the P-site to the amino acid on the tRNA in the A-site.
RBS The ribosomal binding site for mRNA.
Ribosome The complex of RNA and proteins where
proteins are synthesized.
rRNA Ribosomal RNA.
tRNA Transfer RNA, the adaptor RNA molecule that brings
the amino acids to be incorporated into a protein in the
ribosome.
Watson–Crick base pairing A specific hydrogen bonding
arrangement in nucleic acids by which cytosine interacts
with guanine and thymine (or uracil in RNA) interacts
with adenine in a planar arrangement.
Detailed information about the three-dimensional (3D)
structure of the rRNAs has been obtained using X-ray crystal­
lography. The structures of rRNA are highly complex and the
deviations from standard conformation of RNA (A-type RNA)
are numerous. On the one hand, the hydrogen bonding
between bases as well as between bases and ribose hydroxyls
shows extensive possibilities for variation beyond the classical
Watson–Crick interaction. On the other hand, bulges and
loops in the secondary structures can sometimes be accommo­
dated into the helical structures.
In the small subunit, the four domains of the secondary
structure of the 16S RNA form four separate 3D domains,
allowing for significant flexibility of the small subunit. The six
domains identified from the secondary structure of the 23S
RNA are intertwined in a complex way, limiting the flexibility
of the large subunit.
The rRNA requires ribosomal proteins to be folded into the
fully functional ribosome. The ribosomal proteins are
assembled onto the rRNA in a defined order.
Functional Sites
The ribosomal functions are to a large extent closely related to
the rRNA. In fact, the central function of the ribosome, peptidyl
transfer, is primarily associated with the rRNA. The binding of
tRNAs and factors to the ribosome involves extensive parts of
the rRNAs.
Binding of mRNA
The messenger RNA (mRNA) binds centrally on the small
subunit of the ribosome, between its platform and head. In
bacteria, a purine-rich sequence is usually found upstream of
the initiator codon of the mRNAs. These sequences are com­
plementary to a region of the 3′ end of the 16S rRNA. The
binding of this region of the mRNA to the 3′ end of the 16S
doi:10.1016/B978-0-12-374984-0.01337-1
Figure 1 The secondary structure of the ribosomal RNAs from Thermus thermophilus. (a) 16S RNA with four domains emerging from the same central region. (b) 23S RNA and 5S RNA. The six domains (I–VI) are
shown in different colors. The helices are numbered 1–101. (c and d) The three-dimensional structures of the rRNAs of the small and large subunits, respectively. The coloring scheme is the same as in (a) and (b). Notice
the long yellow helix, the penultimate helix (H44) of the small subunit. While the RNA domains in the small subunit are separate folding units, the domains of the large subunit are interwoven. From Yusupov MM,
Yusupova GZh, Baucom A, et al. (2000) Crystal structure of the ribosome at 5.5 Å resolution. Science 292: 883–896. Reprinted with permission from AAAS.
246 Ribosomal RNA
rRNA is often called the Shine–Dalgarno interaction, but the
general interaction is called the ribosome-binding site (RBS).
In eukaryotes, the binding site on the mRNA for
the ribosome is recognized quite differently. The eucaryal
mRNAs usually have a cap, an N7-methylated GTP linked by
a 5′,5′-pyrophosphate bond to the terminal nucleotide. This
cap is recognized by cap-binding proteins that are important
constituents for the binding of the mRNA to the small subunit.
Decoding Site
The decoding of the mRNA by the tRNAs is done on the small
subunit. The anticodons of the tRNAs in the A- and P-sites are
base paired with the corresponding codons of the mRNA. The
fidelity of translation requires a selection of the cognate tRNA
over noncognate or near-cognate tRNAs. The base pairing can­
not sufficiently explain the selectivity. The 16S RNA is closely
associated with the decoding in the A-site of the ribosome.
Crystallographic analyses of the small subunit with codons
interacting with anticodon stem and loop fragments of tRNAs
show that conserved nucleotides from the 16S RNA participate
through hydrogen bonding to the ribose hydroxyls to identify
the Watson–Crick base pairing of the codon–anticodon inter­
actions. This ensures that the cognate tRNA is bound. The
nucleotides of the 16S that participate in this checking function
are A1492 and A1493 as well as G530. They have two confor­
mations, one is the resting conformation and in the other they
are flipped out to interact with the codon and anticodon of the
cognate tRNA.
Peptidyl Transfer Site
The central function of the ribosome is to transfer a growing or
nascent peptide from the peptidyl-tRNA in the P-site to the
amino acid that is bound to the tRNA in the A-site. Peptidyl
transfer occurs on the large ribosomal subunit. A cognate tRNA
is selected in the A-site according to exposed codon of the
mRNA. The peptidyl transfer activity is primarily associated
with the central circle of domain V of the 23S RNA from the
large subunit (Figure 1(b)). The CCA-end of the P-site tRNA
forms base pairs with G2252 and G2253 of the 23S RNA and
G2551 forms a base pair with the CCA-end of the A-site tRNA.
The site for peptidyl transfer is primarily composed of rRNA,
but in bacteria the N-terminus of ribosomal protein L27 is part
of the peptidyl transfer site.
Factor Binding Site
The common binding site for several translation factors includ­
ing elongation factors Tu and G (EF-Tu and EF-G) has
important contributions of rRNA. The main contacts are with
the large ribosomal subunit. One region is helices H42-H44 of
the 23S RNA. This region of the ribosome is also known to bind
ribosomal proteins interacting with the elongation factors (L7/
L12, L10, and L11). Another region is the α-sarcin/ricin loop
(SRL) of the 23S RNA (H95, residues 2653–2667), which
interacts with both elongation factors.
Binding of Antibiotics
Ribosomes are the targets of numerous antibiotics. These inhi­
bitors bind at vital functional sites. In most cases, their binding
sites are on the rRNAs. Furthermore, antibiotic resistance is
frequently due to chemical modification (methylation) of
rRNA in the antibiotic binding site.
See also: Ribosomes.
Further Reading
Ban N, Nissen P, Hansen J, Moore PB, and Steitz TA (2000) The complete atomic
structure of the large ribosomal subunit at 2.4 Å resolution. Science 289: 905–920.
Klein DJ, Schmeing TM, Moore PB, and Steitz TA (2001) The Kink-turn: A new RNA
secondary structure motif. EMBO Journal 20: 4214–4221.
Liljas A and Ehrenberg M (2011) Structural Aspects of Protein Synthesis, 2nd edn.
Singapore: World Scientific.
Moore PB and Steitz TA (2003) The structural basis of large ribosomal subunit function.
Annual Reviews of Biochemistry 72: 813–850.
Roberts E, Sethi A, Montoya J, Woese CR, and Luthey-Schulten Z (2008) Molecular
signatures of ribosomal evolution. Proceedings of the National Academy of Sciences
of the United States of America 105: 13953–13958.
Yusupov MM, Yusupova GZh, Baucom A, et al. (2001) Crystal structure of the ribosome
at 5.5Å resolution. Science 292: 883–896.
Relevant Websites
http://bioinformatics.psb.ugent.be – Bioinformatics and Systems Biology.
http://www.arb-silva.de/ – SILVA comprehensive ribosomal RNA databases.
http://en.wikipedia.org/wiki/Ribosomal_RNA – Wikipedia: The Free Encyclopedia.