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Gene Review

RNASE1  -  ribonuclease, RNase A family, 1 (pancreatic)

Homo sapiens

Synonyms: HP-RNase, RAC1, RIB-1, RIB1, RNS1, ...
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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


Chemical compound and disease context of RNASE1


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


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


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


  1. Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction. Suzuki, M., Saxena, S.K., Boix, E., Prill, R.J., Vasandani, V.M., Ladner, J.E., Sung, C., Youle, R.J. Nat. Biotechnol. (1999) [Pubmed]
  2. Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity. Boix, E., Wu, Y., Vasandani, V.M., Saxena, S.K., Ardelt, W., Ladner, J., Youle, R.J. J. Mol. Biol. (1996) [Pubmed]
  3. X-ray structure of two crystalline forms of a streptomycete ribonuclease with cytotoxic activity. Sevcik, J., Urbanikova, L., Leland, P.A., Raines, R.T. J. Biol. Chem. (2002) [Pubmed]
  4. Glycosylation of human pancreatic ribonuclease: differences between normal and tumor states. Peracaula, R., Royle, L., Tabares, G., Mallorqui-Fernández, G., Barrabés, S., Harvey, D.J., Dwek, R.A., Rudd, P.M., de Llorens, R. Glycobiology (2003) [Pubmed]
  5. Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders. Tanaka, S., Liu, L., Kimura, J., Shiojiri, S., Takahashi, Y., Kitaguchi, N., Nakamura, S., Ueda, K. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  6. "Chitin Leash": a polysaccharide heterobifunctional cross-linking agent which can be cleaved by lysozyme. Guan, K., Cecchini, D.J., Giese, R.W. Carbohydr. Res. (1993) [Pubmed]
  7. Eukaryotic ribonuclease P: a plurality of ribonucleoprotein enzymes. Xiao, S., Scott, F., Fierke, C.A., Engelke, D.R. Annu. Rev. Biochem. (2002) [Pubmed]
  8. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Ridanpää, M., van Eenennaam, H., Pelin, K., Chadwick, R., Johnson, C., Yuan, B., vanVenrooij, W., Pruijn, G., Salmela, R., Rockas, S., Mäkitie, O., Kaitila, I., de la Chapelle, A. Cell (2001) [Pubmed]
  9. Human milk samples from different ethnic groups contain RNase that inhibits, and plasma membrane that stimulates, reverse transcription. Das, M.R., Padhy, L.C., Koshy, R., Sirsat, S.M., Rich, M.A. Nature (1976) [Pubmed]
  10. Three-dimensional models of the tRNA-like 3' termini of some plant viral RNAs. Rietveld, K., Pleij, C.W., Bosch, L. EMBO J. (1983) [Pubmed]
  11. Subcellular localization of low-abundance human immunodeficiency virus nucleic acid sequences visualized by fluorescence in situ hybridization. Lawrence, J.B., Marselle, L.M., Byron, K.S., Johnson, C.V., Sullivan, J.L., Singer, R.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  12. Characterization of genetic variation and 3'-azido-3'-deoxythymidine- resistance mutations of human immunodeficiency virus by the RNase A mismatch cleavage method. López-Galíndez, C., Rojas, J.M., Nájera, R., Richman, D.D., Perucho, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  13. Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. van Ginkel, P.R., Gee, R.L., Shearer, R.L., Subramanian, L., Walker, T.M., Albert, D.M., Meisner, L.F., Varnum, B.C., Polans, A.S. Cancer Res. (2004) [Pubmed]
  14. Crosstalk between extrinsic and intrinsic cell death pathways in pancreatic cancer: synergistic action of estrogen metabolite and ligands of death receptor family. Basu, A., Castle, V.P., Bouziane, M., Bhalla, K., Haldar, S. Cancer Res. (2006) [Pubmed]
  15. Mutational analysis of the complex of human RNase inhibitor and human eosinophil-derived neurotoxin (RNase 2). Teufel, D.P., Kao, R.Y., Acharya, K.R., Shapiro, R. Biochemistry (2003) [Pubmed]
  16. Anti-tumor effect of hematopoietic cells carrying the gene of ribonuclease inhibitor. Fu, P., Chen, J., Tian, Y., Watkins, T., Cui, X., Zhao, B. Cancer Gene Ther. (2005) [Pubmed]
  17. Toxicity of an antitumor ribonuclease to Purkinje neurons. Newton, D.L., Walbridge, S., Mikulski, S.M., Ardelt, W., Shogen, K., Ackerman, S.J., Rybak, S.M., Youle, R.J. J. Neurosci. (1994) [Pubmed]
  18. Gene organization of the human high affinity receptor for IgG, Fc gamma RI (CD64). Characterization and evidence for a second gene. van de Winkel, J.G., Ernst, L.K., Anderson, C.L., Chiu, I.M. J. Biol. Chem. (1991) [Pubmed]
  19. Human ribonuclease A superfamily members, eosinophil-derived neurotoxin and pancreatic ribonuclease, induce dendritic cell maturation and activation. Yang, D., Chen, Q., Rosenberg, H.F., Rybak, S.M., Newton, D.L., Wang, Z.Y., Fu, Q., Tchernev, V.T., Wang, M., Schweitzer, B., Kingsmore, S.F., Patel, D.D., Oppenheim, J.J., Howard, O.M. J. Immunol. (2004) [Pubmed]
  20. Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity. Domachowske, J.B., Dyer, K.D., Adams, A.G., Leto, T.L., Rosenberg, H.F. Nucleic Acids Res. (1998) [Pubmed]
  21. Compensating effects on the cytotoxicity of ribonuclease A variants. Dickson, K.A., Dahlberg, C.L., Raines, R.T. Arch. Biochem. Biophys. (2003) [Pubmed]
  22. Human endothelial cells selectively express large amounts of pancreatic-type ribonuclease (RNase 1). Landré, J.B., Hewett, P.W., Olivot, J.M., Friedl, P., Ko, Y., Sachinidis, A., Moenner, M. J. Cell. Biochem. (2002) [Pubmed]
  23. Preparation of potent cytotoxic ribonucleases by cationization: enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups. Futami, J., Maeda, T., Kitazoe, M., Nukui, E., Tada, H., Seno, M., Kosaka, M., Yamada, H. Biochemistry (2001) [Pubmed]
  24. Ribonucleases of human serum, urine, cerebrospinal fluid, and leukocytes. Activity staining following electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Blank, A., Dekker, C.A. Biochemistry (1981) [Pubmed]
  25. Characterization of the tryptophan residues of human placental ribonuclease inhibitor and its complex with bovine pancreatic ribonuclease a by steady-state and time-resolved emission spectroscopy. Sardar, P.S., Maity, S.S., Ghosh, S., Chatterjee, J., Maiti, T.K., Dasgupta, S. The journal of physical chemistry. B, Condensed matter, materials, surfaces, interfaces & biophysical. (2006) [Pubmed]
  26. The role of lysine-41 of ribonuclease A in the interaction with RNase inhibitor from human placenta. Blackburn, P., Gavilanes, J.G. J. Biol. Chem. (1980) [Pubmed]
  27. Eosinophil-derived neurotoxin and human liver ribonuclease. Identity of structure and linkage of neurotoxicity to nuclease activity. Sorrentino, S., Glitz, D.G., Hamann, K.J., Loegering, D.A., Checkel, J.L., Gleich, G.J. J. Biol. Chem. (1992) [Pubmed]
  28. Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K. Yang, J.P., Reddy, T.R., Truong, K.T., Suhasini, M., Wong-Staal, F. Oncogene (2002) [Pubmed]
  29. Posttranscriptional control of renin synthesis: identification of proteins interacting with renin mRNA 3'-untranslated region. Skalweit, A., Doller, A., Huth, A., Kähne, T., Persson, P.B., Thiele, B.J. Circ. Res. (2003) [Pubmed]
  30. A 40-bp RNA element that mediates stabilization of vascular endothelial growth factor mRNA by HuR. Goldberg-Cohen, I., Furneauxb, H., Levy, A.P. J. Biol. Chem. (2002) [Pubmed]
  31. A nuclear SH3 domain-binding protein that colocalizes with mRNA splicing factors and intermediate filament-containing perinuclear networks. Craggs, G., Finan, P.M., Lawson, D., Wingfield, J., Perera, T., Gadher, S., Totty, N.F., Kellie, S. J. Biol. Chem. (2001) [Pubmed]
  32. Alternative splicing of the mRNA encoding the human cholesteryl ester transfer protein. Inazu, A., Quinet, E.M., Wang, S., Brown, M.L., Stevenson, S., Barr, M.L., Moulin, P., Tall, A.R. Biochemistry (1992) [Pubmed]
  33. Proteasomal RNase activity in human epidermis. Horikoshi, T., Page, J., Lei, G., Brysk, H., Arany, I., Tyring, S.K., Brysk, M.M. In Vivo (1998) [Pubmed]
  34. Expression of human placental ribonuclease inhibitor in Escherichia coli. Lee, F.S., Vallee, B.L. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  35. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. Tahbaz, N., Kolb, F.A., Zhang, H., Jaronczyk, K., Filipowicz, W., Hobman, T.C. EMBO Rep. (2004) [Pubmed]
  36. The human transcriptional repressor protein NAB1: expression and biological activity. Thiel, G., Kaufmann, K., Magin, A., Lietz, M., Bach, K., Cramer, M. Biochim. Biophys. Acta (2000) [Pubmed]
  37. Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells. Nakata, S., Yoshida, T., Horinaka, M., Shiraishi, T., Wakada, M., Sakai, T. Oncogene (2004) [Pubmed]
  38. Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Dohrman, A., Miyata, S., Gallup, M., Li, J.D., Chapelin, C., Coste, A., Escudier, E., Nadel, J., Basbaum, C. Biochim. Biophys. Acta (1998) [Pubmed]
  39. Selective abolition of pancreatic RNase binding to its inhibitor protein. Kumar, K., Brady, M., Shapiro, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  40. Ribonuclease k6: chromosomal mapping and divergent rates of evolution within the RNase A gene superfamily. Deming, M.S., Dyer, K.D., Bankier, A.T., Piper, M.B., Dear, P.H., Rosenberg, H.F. Genome Res. (1998) [Pubmed]
  41. An RNasin-resistant ribonuclease selective for interleukin 2 mRNA. Hua, J., Garner, R., Paetkau, V. Nucleic Acids Res. (1993) [Pubmed]
  42. Purification of mammalian ribonuclease using immobilized human ribonuclease inhibitor. Nadano, D., Yasuda, T., Takeshita, H., Sawazaki, K., Kishi, K. Protein Expr. Purif. (1996) [Pubmed]
  43. Luteinization-associated changes in protein stability of the regulatory subunit of the type I cAMP-dependent protein kinase. Jackiw, V., Hunzicker-Dunn, M. J. Biol. Chem. (1992) [Pubmed]
  44. Imaging the binding ability of proteins immobilized on surfaces with different orientations by using liquid crystals. Luk, Y.Y., Tingey, M.L., Dickson, K.A., Raines, R.T., Abbott, N.L. J. Am. Chem. Soc. (2004) [Pubmed]
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