Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) are capable of suppressing the host cell protein synthesis even without viral gene expression. This phenomenon is known as the early shutoff or as the virion-associated host shutoff (vhs) to emphasize that it is mediated by a component of infecting virions which is a product of the UL41 (vhs) gene. The UL41 encoded protein is a functional tegument protein also present in light (L) particles and is not essential for virus replication. The major product of UL41 gene is a 58 K phosphoprotein. At least two forms of UL41 protein differing in the extent of phosphorylation are present in HSV-1-infected cells. HSV-2 compared to HSV-1 strains display a stronger vhs phenotype. However, in superinfection experiments the less strong vhs phenotype is dominant. UL41 protein triggers disruption of polysomes and rapid degradation of all host and viral mRNAs and blocks a reporter gene expression without other HSVs proteins. The available evidence suggests that UL41 protein is either itself a ribonuclease (RNase) or a subunit of RNase that contains also one or more cellular subunits. UL41 protein is capable of interacting with a transactivator of an alpha-gene, the alpha-transinducing factor (alpha-TIF). Interaction of UL41 protein with alpha-TIF down regulates the UL41 (vhs) gene activity during lytic infection. The possible role of other viral proteins in the shutoff is discussed.
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PMID:Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. 1208 25

Spring viremia of carp (SVC) is an important disease affecting cyprinids, mainly common carp Cyprinus carpio. The disease is widespread in European carp culture, where it causes significant morbidity and mortality. Designated a notifiable disease by the Office International des Epizooties, SVC is caused by a rhabdovirus, spring viremia of carp virus (SVCV). Affected fish show destruction of tissues in the kidney, spleen and liver, leading to hemorrhage, loss of water-salt balance and impairment of immune response. High mortality occurs at water temperatures of 10 to 17 degrees C, typically in spring. At higher temperatures, infected carp develop humoral antibodies that can neutralize the spread of virus and such carp are protected against re-infection by solid immunity. The virus is shed mostly with the feces and urine of clinically infected fish and by carriers. Waterborne transmission is believed to be the primary route of infection, but bloodsucking parasites like leeches and the carp louse may serve as mechanical vectors of SVCV. The genome of SVCV is composed of a single molecule of linear, negative-sense, single-stranded RNA containing 5 genes in the order 3'-NPMGL-5' coding for the viral nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and polymerase, respectively. Polyacrylamide gel electrophoresis of the viral proteins, and sequence homologies between the genes and gene junctions of SVCV and vesicular stomatitis viruses, have led to the placement of the virus as a tentative member of the genus Vesiculovirus in the family Rhabdoviridae. These methods also revealed that SVCV is not related to fish rhabdoviruses of the genus Novirhabdovirus. In vitro replication of SVCV takes place in the cytoplasm of cultured cells of fish, bird and mammalian origin at temperatures of 4 to 31 degrees C, with an optimum of about 20 degrees C. Spring viremia of carp can be diagnosed by clinical signs, isolation of virus in cell culture and molecular methods. Antibodies directed against SVCV react with the homologous virus in serum neutralization, immunofluorescence, immunoperoxidase, or enzyme-linked immunosorbent assays, but they cross-react to various degrees with the pike fry rhabdovirus (PFR), suggesting the 2 viruses are closely related. However, SVCV and PFR can be distinguished by certain serological tests and molecular methods such as the ribonuclease protection assay.
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PMID:Spring viremia of carp (SVC). 1255 53

Increasing evidence based on pharmacological and genetic studies suggests that retinoid signaling plays an important role in developmental control of striatal neurons. In the present report, we screened for genes that might be regulated by retinoids in the developing striatum. We cultured tissue explants from the lateral ganglionic eminence (striatal primordium), and for regional comparison, its adjacent structures of the cerebral cortex and the medial ganglionic eminence in embryonic day 15 rat telencephalon. Using the ribonuclease protection assay, we found that both all-trans retinoic acid and 9-cis retinoic acid significantly up-regulated dopamine D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein mRNAs in the lateral ganglionic eminence culture. By contrast, neither all-trans retinoic acid nor 9-cis retinoic acid significantly altered D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein mRNAs in the cortical and the medial ganglionic eminence cultures except that D1 receptor mRNA was dramatically induced in the medial ganglionic eminence by retinoic acid treatments. To test whether the induction of multiple dopamine signaling molecules in the lateral ganglionic eminence was due to a general enhancement of neuronal differentiation by retinoic acid, we assayed the effects of retinoic acid on other differentiation markers, including glutamate decarboxylase 65, NR1 subunit of glutamate NMDA receptor and microtubule-associated protein-2. None of these genes were significantly altered by retinoic acid treatments in the lateral ganglionic eminence culture, indicating the specificity of gene regulation by retinoic acid signaling. As D1 receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein are important molecules involved in propagation of striatal dopamine neurotransmission, our study raises the hypothesis that retinoid signaling may coordinately activate the transcriptional program that is associated with the dopamine signaling pathway in developing striatal neurons. Such coordinate regulation by retinoids may be part of the mechanisms by which the complex yet highly organized neurochemical constituents of the striatum are established during development.
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PMID:Regulation of multiple dopamine signal transduction molecules by retinoids in the developing striatum. 1593 42

Nucleolin (NCL) is an abundant stress-responsive, RNA-binding phosphoprotein that controls gene expression by regulating either mRNA stability and/or translation. NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation. However, the mechanism by which NCL phosphorylation affects these functions and the identity of the deadenylase involved, remain largely unexplored. Earlier we demonstrated that NCL phosphorylation is vital for cell cycle progression and proliferation, whereas phosphorylation-deficient NCL at six consensus CK2 sites confers dominant-negative effect on proliferation by increasing p53 expression, possibly mimicking cellular DNA damage conditions. In this study, we show that NCL phosphorylation at those CK2 consensus sites in the N-terminus is necessary to induce deadenylation upon oncogenic stimuli and UV stress. NCL-WT, but not hypophosphorylated NCL-6/S*A, activates poly (A)-specific ribonuclease (PARN) deadenylase activity. We further demonstrate that NCL interacts directly with PARN, and under non-stress conditions also forms (a) complex (es) with factors that regulate deadenylation, such as p53 and the ARE-binding protein HuR. Upon UV stress, the interaction of hypophosphorylated NCL-6/S*A with these proteins is favored. As an RNA-binding protein, NCL interacts with PARN deadenylase substrates such as TP53 and BCL2 mRNAs, playing a role in their downregulation under non-stress conditions. For the first time, we show that NCL phosphorylation offers specificity to its protein-protein, protein-RNA interactions, resulting in the PARN deadenylase regulation, and hence gene expression, during cellular stress responses.
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PMID:Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response. 2916 31