Biology Reference
In-Depth Information
the GluR-B subunit, as described earlier. Deamination of adenosine residues that
occur close to splicing junctions can affect the inclusion/exclusion of either
introns or exons. For example, the ADAR2 autoediting site changes a splice
site and consequently generates a nonfunctional protein (Rueter
et al.
, 1999).
In the transcript encoding
, editing within an intron was shown to alter
the conserved adenosine residue at the branch point resulting in retention of the
intron (Beghini
PTPN6
, 2000). The retained intron contains an in-frame stop codon
which is predicted to generate a truncated protein lacking catalytic activity.
Editing can also remove a stop codon altering the protein produced as
occurs with the hepatitis delta virus (HDV) viral proteins p24 and p27 and this
has a crucial role in the life cycle of the HDV (Polson
et al.
, 1996). The viral
genome contains an amber stop codon (UAG) which is altered by A-I editing to
produce a UIG codon which is translated as tryptophan (UGG) by the transla-
tion machinery. The two proteins produced, short (p24) and long (p27), differ by
19 amino acids and have specific roles in the viral life cycle. p24 is required for
replication of the viral RNA genome, whereas p27 represses replication and is
required for packaging of the virus (Polson
et al.
et al.
, 1996). Editing can also result in
the exonization of
Alu
elements via generation of splice site consensus sequences
(Athanasiadis
, 2004).
Editing of noncoding regions is widespread (Li
et al.
, 2009); however,
little is known about the effects of these editing events. Editing within 3
0
UTR
regions could potentially alter polyadenylation signal sequences; however, this
has yet to be reported. Editing can also alter miRNA binding sites thereby
altering their target specificity (Borchert
et al.
, 2009). Over 3000 of the 12,723
editing events that were analyzed in this study formed 7-mer seed matches to a
subset of human miRNAs. They also found that in 200 of the ESTs that editing
within a specific 13 nucleotide motif created seed matches to three otherwise
unrelated miRNAs.
The formation of one or many I-U base pairs in dsRNA can have
structural implications as I-U base pairing is less stable than A-U pairing, and
has a lower melting temperature (Serra
et al.
, 2004). I-U base pairs can alter the
stacking of the dsRNA helix and in hyperedited transcripts these changes are
likely to have a more substantial effect.
Hyperediting of dsRNA transcripts, where up to 50% of the adenosine
residues in a single transcript are deaminated to inosines, has been observed
in vitro
et al.
for perfect RNA duplexes. However, hyperedited transcripts can also
occur
, an example being the voltage-dependent potassium channel
(sqKv2) RNA from squid, where up to 17 adenosines are modified in a 360-
base region (Patton
in vivo
, 1997). Hyperedited RNAs are cleaved by Tudor
staphylococcal nuclease (Tudor-SN) protein, a component of the RNA-induced
silencing complex (RISC). Tudor-SN specifically binds to inosine-containing
RNA and promotes cleavage at the cleavage site (5
0
-IIUI-3
0
)(Scadden, 2005).
et al.
