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)

Interferon-inducible ribonuclease L (RNase L) is a unique ankyrin-repeat containing endoribonuclease activated by 2',5'-oligoadenylate (2-5A) cofactor leading to RNA degradation and apoptosis during antiviral response in mammalian cells. We report that expression of recombinant human RNase L (1-741 a.a.) caused RNA degradation and inhibition of cell growth in Escherichia coli in absence of exogenous 2-5A. On the contrary, expression of a homologous but dominant negative form of murine RNase L (1-656 a.a.), lacking the RNA binding and ribonuclease domain, did not show RNA degradation, rather it stimulated cell growth. Upon computational analysis by pBLAST search, a putative transcription factor (yahD, F64758, and NP_414852) from the E. coli genome showed highest homology (E value=1e(-17)) with 90-259 a.a. region of human RNase L due to ankyrin repeats with conserved GKT motifs. Ankyrin repeats 6-9 of RNase L are involved in 2-5A binding, dimerization, and activation of the ribonuclease. Thus, a biochemically active human RNase L in E. coli strongly suggests for a prokaryotic cell growth-inhibitory mechanism possibly through ankyrin-ankyrin interaction of YahD and RNase L leading to RNA degradation. The mammalian interferon-inducible RNase L and E. coli yahD protein may have common origin for the ankyrin repeats with 2-5A binding sites. Thus, RNA degradation and cell growth inhibition by recombinant human RNase L biochemically reconstituted mammalian cellular response to interferon in E. coli. RNase L has prokaryotic evolutionary history, it is not only an antiviral but also an antibacterial gene.
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PMID:Expression of interferon-inducible recombinant human RNase L causes RNA degradation and inhibition of cell growth in Escherichia coli. 1506 98

The neurodegenerative process in HIV encephalitis (HIVE) is associated with extensive damage to the dendritic and synaptic structure that often leads to cognitive impairment. Several mechanisms might be at play, including release of neurotoxins, oxidative stress and decreased activity of neurotrophic factors. Furthermore, HIV-mediated dysregulation of genes involved in neuronal maintenance might play an important role. For this purpose, cRNA was prepared from the brains of 17 AIDS patients for analysis with the Affymetrix Human U95Av2 GeneChip and analyzed with the GeneSpring Expression Analysis Software. Out of 12,625 genes analyzed, 74 were downregulated and 59 were upregulated compared to controls. Initial alternative analysis of RNA was performed by ribonuclease protection assay (RPA). In cases with HIVE, downregulated genes included neuronal molecules involved in synaptic plasticity and transmission (ion channels, synaptogyrin, synapsin II), cell cycle (p35, p39, CDC-L2, CDC42, PAK1) and signaling molecules (PI3K, Ras-Raf-MEK1), transcription factors and cytoskeletal components (MAP-1B, MAP-2, tubulin, adducin-2). Upregulated genes included those involved in neuroimmune (IgG, MHC, beta2microglobulin) and anti-viral responses (interferon-inducible molecules), transcription (STAT1, OLIG2, Pax-6) and signaling modulation (MEK3, EphB1) of the cytoskeleton (myosin, aduccin-3, radixin, dystrobrevin). Taken together, this study suggests that HIV proteins released from infected macrophages might not only induce a neuroinflammatory response, but also may promote neurodegeneration by interfering with neuronal transcription of genes involved in regulating signaling and cytoskeletal molecules important in maintaining synapto-dendritic functioning and integrity.
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PMID:Patterns of gene dysregulation in the frontal cortex of patients with HIV encephalitis. 1557 94

The latent ribonuclease RNase L and the interferon-inducible 2',5'-oligoadenylate synthetase (OAS) have been implicated in the antiviral response against hepatitis C virus (HCV). However, the specific roles of these enzymes against HCV have not been fully elucidated. In this study, a scarce endogenous expression and RNA degrading activity of RNase L in human hepatoma Huh7 cells enabled us to demonstrate the antiviral activity of RNase L against HCV replication through the transient expression of the enzyme. The antiviral potential of specific members of the OAS family was further examined through overexpression and RNA interference approaches. Our data suggested that among the members of the OAS family, OAS1 p46 and OAS3 p100 mediate the RNase L-dependent antiviral activity against HCV.
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PMID:The ribonuclease L-dependent antiviral roles of human 2',5'-oligoadenylate synthetase family members against hepatitis C virus. 2319 81

RNase L is a cellular endoribonuclease that is activated by 2',5'-linked oligoadenylates (2-5A), which are unique and specific ligands synthesized by a family of interferon-inducible, dsRNA-activated enzymes named oligoadenylate synthetases. In the typical antiviral pathway, activated RNase L degrades viral and cellular RNAs, thus limiting viral replication and spread. Although the antiviral activity of RNase L has been demonstrated for several RNA viruses, there is little evidence regarding its role against DNA viruses. In the present study, the potential antiviral activity of RNase L against hepatitis B virus (HBV) was explored utilizing the recently reported infection protocol based on human hepatoma HepG2 cells stably complemented with the virus entry factor NTCP. Viral replication and expression in this cell type was markedly inhibited by poly(I:C)- or 2-5A-mediated activation of RNase L; however, the inhibition was significantly reversed by RNase L knockdown. Further analysis in HBV1.2-transfected Huh-7 hepatoma cells indicated that the antiviral activity of RNase L depends on its ribonuclease function. We also provide evidence for the specific roles of OAS family members in this process. These results suggest that HBV replication can be regulated through interferon-mediated RNA decay pathways and that activation of these host antiviral factors may represent a novel therapeutic strategy for HBV infection.
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PMID:Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L. 2450 40