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Chen
et al. Vet Res (2021) 52:73
associated protein (NSAP1) or heterogeneous nuclear
ribonucleoproteins (hnRNP Q).
SYNCRIP is a highly
conserved cytoplasmic RNA-binding protein, which
plays important roles in neuronal, myeloid leukemia
stem cell and muscular development [
11
,
12
]. Abnor-
mal expression of SYNCRIP
is associated with immune
response disorders and neuro-degenerative disorders
[
13
–
15
]. In addition, SYNCRIP is implicated as a key
factor in the morphology
and growth of the neuromus-
cular junction and regulation of cytoplasmic vesicle-
based messenger RNA (mRNA) transport in the fly
embryo [
16
]. SYNCRIP can interact with a lot of RNA
sequence, such as UAUC [
17
], poly(A) [
18
], hEXO
(GGCU/A) [
19
] and regulate the edition, sorting,
Figure 1 PPV transcription map. A PPV genome. Linear single-stranded negative PPV genome is shown. ITR, inverted terminal repeat.
B Different
open reading frames are indicated with different colors.
C Different RNA encoding different viral proteins.
Page 3 of 15
Chen
et al. Vet Res (2021) 52:73
degradation, transportation and translation of RNA
[
20
,
21
]. SYNCRIP has a similar
structure to the RNA
binding protein family (RBM), which contains three
conserved RNA recognition motif (RRM) domains-
RRM1, RRM2, and RRM3. It contains seven high-con-
fidence RNA-bound peptides mapped to RRM 1, 2 and
3 using the RBDmap data set [
19
], and two high-confi-
dence and five candidate
RNA-bound peptides mapped
to the amino N-terminal region of SYNCRIP [
19
]. The
highly conserved N-terminal domain can interact with
Apobec protein [
22
], while an irregularity, less con-
served C-terminus can mediate the interaction with
synaptotagmins [
23
]. Previous studies have found that
RNA binding protein RBM38 and RBM45 regulate the
expression of the 11 kDa protein of Parvovirus B19 to
promote viral replication [
24
,
25
]. SYNCRIP has been
reported to be exploited by virus
to promote viral repli-
cation, for example, RNA Hepatitis C virus (HCV) and
mouse hepatitis virus (MHV) can bind with SYNCRIP
to promote virus RNA replication [
26
,
27
]. However,
there is no report whether SYNCRIP is involved in reg-
ulating the formation of viral non-structural proteins.
In
this study, we attempted to explore the mecha-
nism of NS1 mRNA alternative splicing to produce NS2
mRNA. Using RNA-pulldown and mass spectrometry
analysis, we identified and characterized a PPV NS1
mRNA-binding protein SYNCRIP. We also identified
the roles of SYNCRIP in alternative splicing of NS1
mRNA to form NS2 mRNA and in modulation of NS1/
NS2
ratio and PPV DNA replication, and determined
the action sites of SYNCRIP on NS1 mRNA. Our pro-
posed mechanism of SYNCRIP-mediating PPV NS1
mRNA splicing would provide potential targets for
antiviral intervention and reveal
a novel host function
for this protein.
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