Syncrip facilitates porcine parvovirus viral dna replication through the alternative splicing of ns1 mrna to promote ns2 mrna formation

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Open Access

Songbiao Chen and Bichen Miao contributed equally to this work
College of Veterinary Medicine, Northwest A&F University, Yangling, China

Page 2 of 15
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 [

]. Abnor-
mal expression of SYNCRIP is associated with immune 
response disorders and neuro-degenerative disorders 

]. 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 [
]. SYNCRIP can interact with a lot of RNA 
sequence, such as UAUC [
], poly(A) [
], hEXO 
(GGCU/A) [
] 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 

]. 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 [
], and two high-confi-
dence and five candidate RNA-bound peptides mapped 
to the amino N-terminal region of SYNCRIP [
]. The 
highly conserved N-terminal domain can interact with 
Apobec protein [
], while an irregularity, less con-
served C-terminus can mediate the interaction with 
synaptotagmins [
]. 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 [

]. 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 [

]. 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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