The process of A-to-I editing is particularly prevalent in humans, where it occurs in approximately 1000 genes. Enzymes called ADARs (adenosine deaminases acting on RNA) perform this type of editing; these enzymes recognize a double-stranded RNA structure that is formed through base-pairing between the site to be edited and a complementary sequence located elsewhere on the same RNA molecule, typically in an intron (Figure 7–60). The structure of the double-stranded RNA specifies whether the mRNA is to be edited, and if so, where the edit should be made. An especially important example of A-to-I editing takes place in the mRNA that codes for a transmitter-gated ion channel in the brain. A single edit changes a glutamine to an arginine; the affected amino acid lies on the inner wall of the channel, and the editing change alters the Ca2+ permeability of the channel. Mutant mice that cannot make this edit are prone to epileptic seizures and die during or shortly after weaning, showing that editing of the ion channel RNA is normally crucial for proper brain development.
C-to-U editing, which is carried out by a different set of enzymes, is also crucial in mammals. For example, in certain cells of the gut, the mRNA for apolipoprotein B undergoes a C-to-U edit that creates a premature stop codon and therefore
Figure 7–59 Regulation of the site of RNA cleavage and poly-A addition determines whether an antibody molecule is secreted or remains membrane-bound. in unstimulated B lymphocytes (left), a long rnA transcript is produced, and the intron sequence (yellow) near its 3ʹ end is removed by rnA splicing to provide an mrnA molecule that codes for a membrane-bound antibody molecule. Only a portion of the antibody gene is shown in the figure; the actual gene and  its mrnA would extend further to the  left of the diagram. After antigen stimulation (right), the rnA transcript is cleaved and polyadenylated upstream from the intron’s 3′ splice site. As a result, some of the intron sequence remains as a coding sequence in the short transcript and specifies the hydrophilic C-terminal portion of the secreted antibody molecule (brown). (Adapted from D. Di Giammartino et al., Mol. Cell 43:853–866, 2011. with permission from elsevier.)
Figure 7–60 Mechanism of A-to-I RNA editing in mammals. typically, a sequence complementary to the position of the edit is present in an intron, and the resulting double-stranded rnA structure attracts an A-to-i editing enzyme (ADAr). in the case illustrated, the edit is made in an exon; in most cases, however, this occurs in noncoding portions of the mrnA. editing by ADAr takes place in the nucleus, before the pre-mrnA has been fully processed. Mice and humans have two ADAr genes: ADR1 is expressed in many tissues and is required in the liver for proper red blood cell development; ADR2 is expressed only in the brain, where it is required for proper brain development.
no editing editing, CAA UAA produces a shorter form of the protein. In cells of the liver, the editing enzyme is not expressed, and the full-length apolipoprotein B is produced. The two protein isoforms have different properties, and each plays a role in lipid metabolism that is specific to the organ that produces it (Figure 7–61).