is performed by specialized families of deaminase enzymesthat catalyze hydrolysis of amino groups on
cytidine and adenosine (Figure 7.23). On a much slower timescale, these same reactions occur spontan-
eously and nonspecifically at A and C, which is one reason why it is challenging to determine the original
sequence of DNA or RNA samples that have been extracted from old biological material (100 years old).
However, the deaminases involved in RNA editing have evolved high specificity for their target sequences
and, together with additional proteins, they form efficient editing complexes that modify only discrete
regions of certain RNA messages.
One example of transversional editing gives rise to variants of the proteinapolipoprotein B. One form of
apolipoprotein B (ApoB-48) is half as long as another common variant (ApoB-100), and the balance between
these proteins in different tissues plays a major role in human cardiovascular health. The ApoB-48 variant
results from a stop codon in the ApoB-mRNA. However, this stop codon is not DNA-encoded, but results
from an RNA editing event, whereby a single cytidine is converted to a uracil by a specialized deaminase
protein that has been named Apobec-1.^43 The conversion of a glutamine CAA codon into the UAA stop
codon results in ApoB-48, while unedited transcripts produce ApoB-100. As in subsequent discoveries of
RNA editing, alteration in amino acid identity was only discerned when protein sequences (or cDNA
sequences, since they are derived from edited RNAs) were compared to the genomic sequence of the organ-
ism. Since the discovery of ApoB editing, numerous other examples of C→U editing have been reported.
There is also evidence that Apobec-like enzymes edit the DNA of genes involved in the immune system.^43
A second class of transversional editing is catalyzed by the ADAR familyof adenosine deaminases.^42
This activity was first noted during biochemical studies on an unusual enzyme that was found to bind to
duplex RNA in vitroand to convert certain adenosines into inosines. A biological function for this type of
enzyme was identified during studies of the human glutamate receptor gene. In neurons, it was noted that
270 Chapter 7
NNNH 2O
RHNO N
RH 3 N OH
HNNOO
RH 2 OHNN NNRNH 2HNN NNRHNN NNRO
H 3 N OHH 2 OHC UAIApobecADARFigure 7.23 The deaminase reactions that are catalyzed by RNA editing enzymes Apobec and ADAR. The Apobec
enzymes catalyze C→U transversions at specific sites and the ADAR enzymes catalyze A→I (inosine)
transversions