Essential Cell Biology 5th edition

RNA and the Origins of Life
261
TABLE 7–4 BIOCHEMICAL REACTIONS THAT CAN BE CATALYZED BY
RIBOZYMES
5′
Activity
Ribozymes
Peptide bond formation in protein
synthesis
RNA splicing
DNA ligation
ribosomal RNA
small nuclear RNAs (snRNAs), self-splicing
RNAs
in vitro selected RNA
5′
3′
+
ribozyme
substrate
RNA
3′
RNA polymerization
RNA phosphorylation
in vitro selected RNA
in vitro selected RNA
BASE-PAIRING BETWEEN
RIBOZYME AND SUBSTRATE
RNA aminoacylation
in vitro selected RNA
RNA alkylation
C–C bond rotation (isomerization)
in vitro selected RNA
in vitro selected RNA
RNA Is Thought to Predate DNA in Evolution
If the evolutionary role for RNA proposed above is correct, the first cells
on Earth would have stored their genetic information in RNA rather than
DNA. And based on the chemical differences between these polynucleotides,
it appears that RNA could indeed have arisen before DNA. Ribose
(see Figure 7–3A), like glucose and other simple carbohydrates, is readily
formed from formaldehyde (HCHO), which is one of the principal products
of experiments simulating conditions on the primitive Earth. The sugar
deoxyribose is harder to make, and in present-day cells it is produced
from ribose in a reaction catalyzed by a protein enzyme, suggesting that
ribose predates deoxyribose in cells. Presumably, DNA appeared on the
scene after RNA, and then proved better suited than RNA as a permanent
repository of genetic information. In particular, the deoxyribose in
its sugar–phosphate backbone makes chains of DNA chemically much
more stable than chains of RNA, so that DNA can grow to greater lengths
without breakage.
The other differences between RNA and DNA—the double-helical structure
of DNA and the use of thymine rather than uracil—further enhance
DNA stability by making the molecule easier to repair. We saw in Chapter
6 that a damaged nucleotide on one strand of the double helix can be
repaired by using the other strand as a template. Furthermore, deamination,
one of the most common detrimental chemical changes occurring
CATALYSIS
5′
5′
3′
3′
cleaved
RNA
+
5′
SUBSTRATE CLEAVAGE
5′
PRODUCT RELEASE
ribozyme
Figure 7–49 A ribozyme is an RNA
molecule that possesses catalytic activity.
The RNA molecule shown catalyzes the
cleavage of a second RNA at a specific
site. Such ribozymes are found embedded
in large RNA genomes—called viroids—
that infect plants, where the cleavage
reaction is one step in the replication of the
viroid. (Adapted ECB5 e7.46/7.49 from T.R. Cech and O.C.
Uhlenbeck, Nature 372:39–40, 1994. With
permission from Macmillan Publishers Ltd.)
3′
3′
Figure 7–50 Could an RNA molecule catalyze
its own synthesis? The process would require that
the RNA catalyze the self-templated amplification
steps shown in Figure 7–48. The red rays represent
the active site of this hypothetical ribozyme.