Biology Reference
In-Depth Information
Transgenic mice overexpressing
ADAR2
under the control of a CMV
promoter developed adult-onset obesity (Singh
, 2007). There was no
alteration in editing levels in transcripts edited normally by ADAR2. The
transgenic mice also expressed the endogenous
et al.
and the level of trans-
genic ADAR2 protein in the brain was only 1.2-fold higher than the endogenous
level, leading to the hypothesis that the observed phenotype was due to mis-
expression of the transgene in tissues that do not normally express
ADAR2
.
Interestingly, the same adult-onset obesity phenotype was observed with trans-
genic mice overexpressing a catalytic site mutant
ADAR2
, indicating the
phenotype was not due to aberrant editing. These data suggest that the catalyti-
cally inactive ADAR2 has another function, probably mediated through RNA-
binding.
ADAR2 E396A
C. ADAR3
The third ADAR identified ADAR3 is only expressed in specific regions of the
brain including the amygdala and thalamus (Melcher
et al.
, 1996). Similar to
other ADAR proteins, it is capable of binding to dsRNA
but is unique in
that it also binds to ssRNA through an N-terminal arginine and lysine-rich
region (R domain) (Fig. 3.2). The protein is catalytically inactive; however,
the conservation of the deaminase domain among vertebrates as shown by amino
acid alignment (Keegan
in vitro
et al.
, 2004) indicates it is under positive selective
pressure.
ADAR3 has been shown to act as an effective competitor by
binding to the same transcripts as ADAR1 and ADAR2 and preventing deami-
nation (Chen
In vitro
, 2000). To date, no known function has been described for
ADAR3; however, as it is conserved, it may act as a competitor of ADAR1 and
ADAR2 in the brain and thereby regulate their editing of particular transcripts.
et al.
IV. TESTIS-EXPRESSED NUCLEAR RNA-BINDING PROTEIN
TENR is expressed in the round spermatids in the testis. TENR was identified in a
screen to find RNA-binding proteins that interact with the 3
0
untranslated region
(UTR) of the
Tenr
/
male
protamine 1
(
Prm1
) RNA (Schumacher
et al.
, 1995).
mice are sterile (Connolly
, 2005). This is due to low sperm counts and a
high incidence of sperm morphological defects indicating that TENR plays a role
in sperm morphogenesis. TENR has dsRBDs but lacks the conserved residues
within the deaminase domain that are essential for catalytic activity indicating it
is not a functional deaminase (Connolly
et al.
,no
other transcripts have been identified that it binds to and the biological function
of TENR remains unclear.
et al.
, 2005; Fig. 3.2). Besides
Prm1
