Disease relevance of RNASE1

• In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase [1].
• To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification [2].
• Ribonuclease (RNase) Sa3 is secreted by the Gram-positive bacterium Streptomyces aureofaciens [3].
• Also herein, RNase Sa3 is shown to be toxic to human erythroleukemia cells in culture [3].
• These glycosylation changes in a tumor-secreted protein, which reflect fundamental changes in the enzymes involved in the glycosylation pathway, open up the possibility of using serum RNase 1 as a tumor marker of pancreatic adenocarcinoma [4].

Psychiatry related information on RNASE1

• We studied, by using the RNase protection technique, the expression of APP mRNAs in brains of Alzheimer's disease (AD) and other neurological disorders with special reference to aging [5].
• In a second preparation, in which [14C]acetic anhydride was used, a longer reaction time was employed for the coupling of Chitin Leash to RNase [6].

High impact information on RNASE1

• Most forms of RNase P are ribonucleoproteins, i.e., they consist of an essential RNA subunit and protein subunits, although the composition of the enzyme in mitochondria and chloroplasts is still under debate [7].
• Ribonuclease P (RNase P) is an essential endonuclease that acts early in the tRNA biogenesis pathway [7].
• RNase P activities have been identified in Bacteria, Archaea, and Eucarya, as well as organelles [7].
• We conclude that mutations in RMRP cause CHH by disrupting a function of RNase MRP RNA that affects multiple organ systems [8].
• Human milk samples from different ethnic groups contain RNase that inhibits, and plasma membrane that stimulates, reverse transcription [9].

Chemical compound and disease context of RNASE1

• We have studied the structure of end-labelled 3'-terminal fragments of turnip yellow mosaic virus RNA and brome mosaic virus RNA 2 with chemical modifications of the adenosine and cytidine residues and with enzymatic digestions using RNase T1, nuclease S1 and the double-strand-specific ribonuclease from cobra venom [10].
• The nuclear focus consisted of newly synthesized HIV RNA as shown by hybridization in the absence of denaturation and by susceptibility to RNase and actinomycin D [11].
• Characterization of genetic variation and 3'-azido-3'-deoxythymidine- resistance mutations of human immunodeficiency virus by the RNase A mismatch cleavage method [12].
• While investigating factors differentially expressed in melanoma cells and normal melanocytes, we identified the receptor tyrosine kinase Axl and found up-regulation of Axl in uveal melanomas and melanoma cell lines by RNase protection, Western analysis, and immunohistochemistry [13].
• RNase protection assay and cell surface receptor analysis by flow cytometry show the up-regulation of members of death receptor family in 2-methoxyestradiol-exposed pancreatic cancer cells [14].

Biological context of RNASE1

• We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites [1].
• Previous studies showed that tight binding of RNase A and angiogenin (Ang) is achieved primarily through interactions of hot spot residues in the 434-460 C-terminal segment of RI with the enzymatic active site; Asp435 of RI forms key hydrogen bonds with the catalytic lysine in both complexes, whereas the other contacts are largely distinctive [15].
• The substrate specificity of angiogenin seems, however, to be more restricted than that of the pancreatic RNase [16].
• We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms) [17].
• Two major transcription initiation sites were identified by RNase protection [18].

Anatomical context of RNASE1

• Eosinophil granules contain an antimicrobial protein known as eosinophil-derived neurotoxin (EDN), which belongs to the RNase A superfamily [19].
• In this study, we show that EDN, and to a lesser extent human pancreatic RNase (hPR), another RNase A superfamily member, activates human dendritic cells (DCs), leading to the production of a variety of inflammatory cytokines, chemokines, growth factors, and soluble receptors [19].
• Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes [20].
• The parameter (k(cat)/K(m))(cyto), which reports on the ability of a ribonuclease to manifest its ribonucleolytic activity in the cytosol, is especially useful in predicting the cytotoxicity of an RNase A variant [21].
• The selective strong release of pancreatic-type RNase by endothelial cells suggests that it is endowed with non-digestive functions and involved in vascular homeostasis [22].

Associations of RNASE1 with chemical compounds

• Human RNase 1 was also modified with ethylenediamine [23].
• The RNase activity of leukocytes displays a molecular weight of 17 000 and exhibits a characteristic dependence of its Rf on the temperature at which samples (in 2% NaDodSO4 without mercaptoethanol) are prepared for electrophoresis [24].
• Human placental ribonuclease inhibitor (hRI) containing six tryptophan (Trp) residues located at positions 19, 261, 263, 318, 375, and 438 and its complex with RNase A have been studied using steady-state and time-resolved fluorescence (298 K) as well as low-temperature phosphorescence (77 K) [25].
• The CD measurements suggest that one or more tyrosine residues of RNase A may be involved in the interaction with inhibitor [26].
• Treatment of EDN, liver RNase, and eosinophil cationic protein with iodoacetic acid at pH 5.5 resulted in inactivation of their RNase activity and also destroyed their neurotoxicity [27].

Physical interactions of RNASE1

• RNase inhibitor (RI) binds diverse proteins in the pancreatic RNase superfamily with extremely high avidity [15].
• RNase treatment did not change the strength of binding of hnRNP K to Sam68 [28].
• RNase degradation assays confirm that 3'-UTR binding proteins are able to protect and stabilize REN mRNA in vitro [29].
• Deletion of the HuR binding site within this 40-bp element as mapped by RNase T1 and lead footprinting uncouples a stabilizing sequence from a destabilizing sequence, thus providing a novel RNA-protein regulatory model that might be exploited to manipulate VEGF expression and hypoxia-induced angiogenesis [30].
• Extraction and subfractionation experiments indicated that SNP70 did not bind directly to DNA but did bind to poly(G)-rich oligonucleotides and was resistant to extraction with non-ionic detergents but was solubilized by treatment with RNase, high salt, or ammonium sulfate [31].

Enzymatic interactions of RNASE1

• RNase protection analysis of tissue RNA confirmed the presence of exon 9 deleted transcripts and showed that they represented a variable proportion of the total CETP mRNA in various human tissues including adipose tissue (25%), liver (33%), and spleen (46%) [32].

Co-localisations of RNASE1

• By means of zymography, we demonstrated, for the first time, that RNase activity persists after dissociation of the proteasome on the gel and that it co-localizes to the same range of molecular weight subunits as the proteinase activity [33].

Regulatory relationships of RNASE1

• Thus, these results confirm that PRI inhibits angiogenin more effectively than RNase A [34].
• Unexpectedly, binding of PPD proteins to Dicer inhibits the RNase activity of this enzyme in vitro [35].
• NAB1 is expressed ubiquitously in human cell lines as shown by RNase protection mapping [36].
• An RNase protection assay demonstrated that HDACIs induced DR5 mRNA markedly but not that of other death receptor family members in Jurkat cells [37].
• Results from in situ hybridization and RNase protection assays showed that P. aeruginosa upregulates MUC 5AC as well as MUC 2 in both bronchial explants and cultured airway epithelial cells [38].

Other interactions of RNASE1

• Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI) [1].
• The K(i) value for RNase A is increased by a factor of >10(8), from 36 fM to >4 microM, and the selectivity factor for ANG is now >10(9) [39].
• Each gene encodes a complete ORF with no less than 86% amino acid sequence identity to human RNase k6 with the eight cysteines and catalytic histidines (H15 and H123) and lysine (K38) typically observed among members of the RNase A superfamily [40].
• To further our understanding of the individual lineages comprising the RNase A superfamily, we have isolated and characterized 10 novel genes orthologous to that encoding human RNase k6 from Great Ape, Old World, and New World monkey genomes [40].
• In partially purified form, this RNase is about 7 times as active on IL2 as on beta-globin mRNA [41].

Analytical, diagnostic and therapeutic context of RNASE1

• Affinity chromatography on immobilized ribonuclease (RNase) inhibitor was developed for purification of mammalian RNase [42].
• However, based on Northern blot analysis and solution hybridization/RNase protection assays, this increase in RI alpha protein was not due to an increase in RI alpha mRNA [43].
• Antibodies to EDN and liver RNase showed identical cross-reactivities in assays of nuclease inhibition and in a radioimmunoassay [27].
• Like onconase, which is an amphibian ribonuclease in Phase III clinical trials as a cancer chemotherapeutic, RNase Sa3 is not inhibited by the cytosolic ribonuclease inhibitor protein [3].
• Ellipsometric measurements indicate identical extents of immobilization of RNase A via the two schemes [44].

References