Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

THE RNA WORLD AND THE ORIGINS OF LIFE
363
RNA
WORLD
3′
5′
5′ 3′
15 billion years ago
big bang
10 5
solar
system
formed
first
cells
with
DNA
first
mammals
Figure 6–88 Time line for the universe, suggesting the early existence of an RNA world of
living systems.
present
5′
3′
threenucleotide
bulge
3′
5′
3′
5′
four-stem
junction
5′
3′
The RNA world hypothesis relies on the fact that, among present-day biological
molecules, RNA is unique in being able to act as both a carrier of genetic information
and as a ribozyme to catalyze chemical reactions. In this section, we dis-
MBoC6 m6.98/6.88
cuss these properties of RNA and how they may have been especially important
in early cells.
5′
3′
Single-Stranded RNA Molecules Can Fold into Highly Elaborate
Structures
We have seen in this chapter that RNA can carry genetic information in mRNAs,
and we saw in Chapter 5 that the genomes of some viruses are composed solely
of RNA. We have also seen that complementary base-pairing and other types of
hydrogen bonds can occur between nucleotides in the same chain of RNA, causing
an RNA molecule to fold up in a unique way determined by its nucleotide
sequence (see, for example, Figures 6–50 and 6–67). Comparisons of many RNA
structures have revealed conserved motifs, short structural elements that are used
over and over again as parts of larger structures (Figure 6–89).
Protein catalysts require a surface with unique contours and chemical properties
on which a given set of substrates can react (discussed in Chapter 3). In
exactly the same way, an RNA molecule with an appropriately folded shape can
serve as a catalyst (Figure 6–90). Like some proteins, many of these ribozymes
work by positioning metal ions at their active sites. This feature gives them a wider
range of catalytic activities than provided by the limited chemical groups of a
polynucleotide chain.
Much of our inference about the RNA world has come from experiments in
which large pools of RNA molecules of random nucleotide sequences are generated
in the laboratory. Those rare RNA molecules with a property specified by the
experimenter are then selected out and studied (Figure 6–91). Such experiments
have created RNAs that can catalyze a wide variety of biochemical reactions (Table
6–5), with reaction rate enhancements only a few orders of magnitude lower than
5′ 3′
hairpin
loop
pseudoknot
Figure 6–89 Some common elements
of RNA structure. Conventional,
complementary base-pairing interactions are
indicated by red “rungs” in double-helical
portions of the RNA.
5′
3′
5′
ribozyme
+
3′
substrate
RNA
BASE-PAIRING
BETWEEN
RIBOZYME AND
SUBSTRATE
5′
3′
5′
SUBSTRATE
CLEAVAGE
3′
5′
3′
5′
PRODUCT
RELEASE
3′
+
cleaved
RNA
ribozyme
Figure 6–90 A ribozyme. This simple RNA molecule catalyzes the cleavage of a second RNA at a specific site. This ribozyme is found embedded
in larger RNA genomes—called viroids—which infect plants. The cleavage, which occurs in nature at a distant location on the same RNA molecule
that contains the ribozyme, is a step in the replication of the viroid genome. Although not shown in the figure, the reaction requires a magnesium ion
positioned at the active site. (Adapted from T.R. Cech and O.C. Uhlenbeck, Nature 372:39–40, 1994. With permission from Macmillan Publishers Ltd.)