Biology Reference
In-Depth Information
residues, ADAR enzymes exhibit local sequence preferences. For example, the 5
0
nearest neighbor preference for ADAR1 is U
¼
A
>
C
>
G, similarly for ADAR2
it is U
G(Lehmann and Bass, 2000).
It is thought that the deamination reaction occurs outside the dsRNA,
with the target adenosine residue rotated or flipped 180
allowing deamination of
the base and minimizing structural disruption (reviewed in Roberts and Cheng,
1998). It was observed that ADAR2 induced changes in 2-aminopurine fluores-
cence of a modified substrate which is consistent with a base-flipping model
(Yi-Brunozzi
¼
A
>
C
¼
et al.
, 2001).
VII. TRANSCRIPTS EDITED BY ADARS
Most of the transcripts that are specifically edited by ADARs are expressed in the
CNS (Table 3.1). Pre-mRNA encoding subunits of glutamate receptors both of
the AMPA and kainite classes are edited; however, there is no editing of pre-
mRNA encoding subunits of the NMDA class of receptor. We have previously
discussed editing of
GluR-B Q/R
and R/G sites, also
GluR-C
and
GluR-D
tran-
scripts are both edited at the R/G site (Lomeli
, 1994). In transcripts encoding
the kainate subunit GluR6, there is editing at two positions that convert amino
acids in transmembrane segment 1 and transmembrane segment 2 (K¨hler
et al.
,
1993). RNA editing at these positions affects calcium permeability of the recep-
tor. Editing of transcripts encoding the kainate subunit GluR5 also affects calcium
permeability (Nutt and Kamboj, 1994). Both edited channels are strongly inhib-
ited by low concentrations of fatty acids, whereas channels that contain a mixture
of edited and unedited isoforms resist inhibition (Wilding
et al.
, 2005). Tran-
scripts encoding the serotonin receptor are also edited and up to 24 different
isoforms can be generated by editing (Burns
et al.
, 1997). The fully edited isoform
displays blunted G-protein coupling and reduced constitutive activity. The po-
tassium channel transcript K(V)1.1 is also edited, and this editing is also found in
the
et al.
Drosophila
ortholog of the gene and is an example of convergent evolution
(Bhalla
, 2004). The consequence of editing on this protein is channel
inactivation. The transcript encoding the inhibitory GABA-type A receptor
(GABA
A
) is also edited at one position in transmembrane segment 3 of
et al.
3
where an isoleucine is converted to methionine (Ohlson
, 2007). Whole
cell recordings in HEK 293 cells reveal that receptors containing the edited
isoform have smaller amplitudes, slower activation, and faster deactivation than
those that contain the unedited isoform. It is likely that editing also affects subunit
assembly. The consequence of editing on the functioning of the other proteins
(Clutterbuck
et al.
et al.
, 2005; Levanon
et al.
, 2005) listed in Table I is unknown.
