Biology Reference
In-Depth Information
Z-DNA binding
dsRBD
NLS
DM
hADAR1p160
(1.226 aa)
hADAR1p110
(931 aa)
hADAR2
(701 aa)
hADAR3
(739 aa)
X
hTENR
(576 aa)
X
hADAT1
(502 aa)
hADAT2
(191 aa)
hADAT3
(351 aa)
X
dsRBD: Double strand
RNA binding domain
DM: catalytic
domain
Z-DNA
binding
NLS
No catalytic function
R enriched domain
Figure 3.2. Proteins domains of ADARs consist of dsRNA (black) which bind dsRNA and the
catalytic deaminase domain (DM; gray box). ADAT1, ADAT2, and ADAT3 have a DM
domain which they also use to bind tRNA. ADAR3, TENR, and ADAT3 are inactive
and that is represented by an (X) in the DM domain. ADAR1 has Z-DNA binding at the
N-terminus domains and ADAR3 contains an R-enriched region at the N-terminus.
whereas the shorter isoform p110 is constitutively expressed (Fig. 3.2). Expres-
sion of ADAR1p150 is regulated by an interferon-inducible promoter which
generates a transcript that utilizes the first methionine, whereas utilization of an
internal start site at methionine 296 generates the p110 isoform (Kawakubo and
Samuel, 2000; Patterson and Samuel, 1995). Both proteins have three dsRBDs
and an unusual NLS that overlaps with the third dsRBD (Strehblow
, 2002).
The p150 isoform is a nucleocytoplasmic shuttling protein; however, its locali-
zation is mainly cytoplasmic due to a nuclear export signal (NES) signal within
the first Z-DNA-binding domain at the amino terminus (Poulsen
et al.
, 2001).
The Z-DNA-binding domains are at the amino terminus so ADAR1p150 has
two, however as translation of ADARp110 starts at methionine 296 it only has
one (Fig. 3.2). These Z-DNA-binding domains allow interaction with non-B-
form RNA (Herbert, 2001, p. 599).
ADAR1 p110 is also a nucleocytoplasmic shuttling protein despite
lacking an NES. Instead, it interacts with the export factor exportin-5 (Exp-5)
and export of ADAR1 is enhanced by binding to dsRNA (Fritz
et al.
, 2009).
Transportin-1 (TRN 1) is the nuclear import factor that interacts with the NSL
present in the third dsRBD and binding to dsRNA abolishes import of ADAR1.
et al.
