Biology Reference
In-Depth Information
There are five known editing sites in the transcript encoding the human
serotonin (5-HT
2C
) receptor which are situated within a dsRNA stem-loop
formed between exon 5 and an ECS in intron 5 (Burns
, 1997). This region
also undergoes alternative splicing with one canonical and two alternative 5
0
splice sites. Examination of editing and splicing in this region of the serotonin
receptor transcript revealed a link between increased numbers of sites edited and
use of the canonical 5
0
et al.
, 2004). As the alternative 5
0
splice sites produce truncated inactive protein, this suggests a link between
editing and production of functional serotonin receptor protein. This effect is
likely due to the disruption of the stem-loop structure which allows access of
splicing factors to the canonical 5
0
splice site; however, editing could also
possibly change splicing regulatory signals. A study of editing in malignant
human gliomas which have hypoediting revealed an increase in the serotonin
5HT
2C
receptor transcripts that utilize the alternative 5
0
splice site and therefore
produce truncated inactive protein (Maas
splice site (Flomen
et al.
, 2001).
Characterization of the human protein tyrosine phosphatase
et al.
PTPN6
gene and its role in acute myeloid leukemia revealed increased expression of an
isoform that retained a 251-bp intron (Beghini
, 2000). Sequence analysis of
this isoform demonstrated that multiple A-to-G mutations were present in the
retained intron: one of these occurred 27 bp upstream of the 3
0
splice site and
converted the branch point adenosine to an inosine residue. Loss of the branch
point adenosine led to retention of the intron, which was confirmed with an
in vitro
et al.
splicing reaction. Furthermore, the retained intron contained an in-frame
stop codon which would generate a truncated protein lacking the phosphatase
domain. The level of the abnormally spliced isoform was significantly higher in
patients at the time of diagnosis than when they had entered remission suggest-
ing a correlation with the disease state.
XVI. COORDINATION OF EDITING AND ALTERNATIVE SPLICING
The carboxy-terminal domain (CTD) of RNAP II is involved in co-coordinating
transcription with RNA processing events such as splicing, 3
0
-end formation and
5
0
-capping (McCracken
, 1997a,b). As editing has to occur prior to splicing
studies were performed to determine if the CTD of RNAP II could also coordi-
nate splicing and editing. A truncated RNA pol II lacking the CTD region
revealed that the CTD is required for efficient editing of the rat
et al.
ADAR2
transcript at the autoediting site (Laurencikiene
et al.
, 2006). Further studies
on the
transcript revealed that the RNA pol II CTD enhanced editing by
preventing premature splicing that would remove the intron required for editing
(Ryman
GluR-B
, 2007). At the Q/R site which is located 24 nucleotides upstream of
a splice donor site the effect was similar in that editing enhanced efficient
et al.
