Disease relevance of SYNCRIP

• As further evidence of the role of GRY-RBP, rat hepatoma cells treated with an antisense oligonucleotide to GRY-RBP demonstrated an increase in C to U editing of endogenous apoB RNA [1].
• Together, these data indicate that NSAP1 modulates IRES-dependent translation of BiP mRNA through an RNA-protein interaction under heat stress conditions [2].
• Chronic pain following whiplash injury and non-specific arm pain (NSAP, previously termed diffuse repetitive strain injury) present clinicians with problems of diagnosis and management [3].
• BACKGROUND: Abdominal pain of uncertain aetiology (non-specific abdominal pain; NSAP) is the commonest reason for emergency surgical admission [4].
• Post-streptococcal glomerulonephritis: studies on the interaction between nephritis strain-associated protein (NSAP), complement and the glomerulus [5].

High impact information on SYNCRIP

• BiP mRNAs were redistributed from the heavy polysome to the light polysome in NSAP1 knockdown cells [2].
• The amount of NSAP1 bound to the BiP IRES increased under heat stress conditions, and the IRES activity of BiP mRNA was increased [2].
• Here we show that a cellular protein, NS1-associated protein 1 (NSAP1), augments HCV mRNA translation through a specific interaction with an adenosine-rich protein-coding region within the HCV mRNA [6].
• An HCV replicon RNA capable of mimicking the HCV proliferation process in host cells was further used to confirm that NSAP1 enhances the translation of HCV mRNA [6].
• An RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5-trisphosphate receptor type 1 mRNA in neuronal dendrites [7].

Biological context of SYNCRIP

• Experiments using recombinant proteins demonstrate that GRY-RBP binds to ACF and inhibits both the binding of ACF to apoB RNA and C to U RNA editing [1].
• By yeast two-hybrid cloning using apobec-1 as bait we identified a 69.6-kDa RNA binding protein, GRY-RBP, that contains 3 RNA-recognition motifs (RRMs) as a novel apobec-1 associating protein [8].
• These results raise the possibility that regulation of mRNA translation or stability by insulin may involve the phosphorylation of SYNCRIP [9].
• The methylation of the C-terminal region of hnRNPQ (NSAP1) is important for its nuclear localization [10].

Anatomical context of SYNCRIP

• In vitro phosphorylation studies revealed that SYNCRIP, once extracted from low density microsomes, can be tyrosine phosphorylated using purified insulin receptor [9].
• Furthermore, the interaction between SYNCRIP and Syt-VII, -VIII, or -IX was revealed by co-immunoprecipitation experiments using COS cells transiently expressing each Syt isoform [11].
• Hence, we propose that pp70 and pp68 likely represent B cell homologs of SLP-76 which facilitate and coordinate B cell activation [12].
• A two-hybrid screen identified a HeLa cell cDNA clone (NS1-associated protein 1 [NSAP1]) that interacts with NS11-276 and NS11-638 [13].
• Short interfering RNA-mediated gene-specific knockdown of CUGBP2, GRY-RBP, and hnRNP-C1 resulted in increased editing in Caco-2 cells, consistent with their known inhibitory function [14].

Associations of SYNCRIP with chemical compounds

• However, the induction was not inhibited by HA-1004 and H-8, relatively high-affinity inhibitors of protein kinase A. Phorbol myristate acetate and 1-oleoyl-2-acetyl-sn-glycerol, activators of protein kinase C, were able to induce pp68 in mouse peritoneal macrophages [15].
• The fimbria-induced pp68 was inhibited dramatically by staurosporine, a potent inhibitor of protein kinase C. pp68 induction was also inhibited by H-7, a potent inhibitor of several types of protein kinase [15].

Physical interactions of SYNCRIP

• GRY-RBP was shown to bind to apobec-1, the catalytic component of apoB mRNA editosome, in vivo and in vitro [8].

Other interactions of SYNCRIP

• ACF and GRY-RBP colocalize in the nucleus of transfected cells and, in cotransfection experiments with apobec-1, each appears to colocalize in a predominantly nuclear distribution [1].
• Of relevance, cells transfected with RETMEN2B examined for anti-phosphotyrosine bound proteins, showed other proteins implicated in splicing: DEAD-box p68 RNA helicase, SYNCRIP, and hnRNP K [16].
• Several well known components of FGFR-1 signaling were identified along with two novel candidates: NS-1-associated protein-1 and target of Myb 1-like protein [17].

Analytical, diagnostic and therapeutic context of SYNCRIP

• In this present study we have identified, by MALDI mass spectrometry, pp68 as the tyrosine-phosphorylated form of synaptotagmin-binding cytoplasmic RNA-interacting protein (SYNCRIP)/NSAP1, a newly discovered cytoplasmic RNA-binding protein [9].
• The aim of this study was to examine the role of early laparoscopy in the management of NSAP [4].
• In this way we performed gasless laparoscopic surgery on 54 patients: cholecystectomy (n = 37), abdominal exploration for NSAP (n = 5) or tumor staging (n = 4), fenestration of liver cysts (n = 5), and appendectomy (n = 3) [18].
• Of the 49 patients with SAP, 39 developed pancreatic or peripancreatic NSAP were reactive to skin tests on the third week, while 4% remained anergic necrosis and were operated [19].
• SDS-PAGE and double immunodiffusion analysis showed that no NSAP occurred in the extracellular product of S. pyogenes strain Su [20].

References