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Gene Review

RNH1  -  ribonuclease/angiogenin inhibitor 1

Homo sapiens

Synonyms: PRI, Placental RNase inhibitor, Placental ribonuclease inhibitor, RAI, RNH, ...
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Disease relevance of RNH1


Psychiatry related information on RNH1

  • Alzheimer's disease brain: alterations in RNA levels and in a ribonuclease-inhibitor complex [6].
  • The comprehensive massage therapy group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the other 3 groups [7].
  • On the other hand, PRI mean showed significant differences dependent on age and was inversely correlated with alcohol consumption and X-ray exposure [8].
  • Assessments included socio-demographic variables and health status measures (MHAQ, AIMS2, SF-36, fatigue and pain on VAS 0-100 mm, self efficacy, and RAI as a measure for helplessness) [9].
  • Four groups of subjects were compared with respect to their clinical and demographic status and electroencephalographic (EEG) characteristics, namely: primary major depressive disorder (PRI MDD); panic disorder (Panic); "Mixed" group comprising patients meeting full syndromal criteria for MDD and panic occurring concomitantly; and normal controls [10].

High impact information on RNH1


Chemical compound and disease context of RNH1


Biological context of RNH1

  • 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 [21].
  • However, multisite mutagenesis of RI reveals strong superadditivity of mutational effects, indicating that part of this shortfall reflects negative cooperativity [21].
  • The RNH1 gene is contained within an open reading frame (ORF) predicted to encode a protein of 53.7 kDa [22].
  • The C-terminal amino acid sequence deduced from the cDNA is identical to the peptide sequence obtained from a CNBr fragment of RAI, confirming the identity of the clone [23].
  • The deduced primary structure of RAI consists of eight homologous tandem repeats with remarkable periodicity of leucine and cysteine residues [23].

Anatomical context of RNH1

  • These data are consistent with the finding of two species of mRNA for hFc gamma RI in myeloid cells that are upregulated when cultured with gamma-interferon [24].
  • Eukaryotic cells exposed to mammalian ribonucleases are protected from their cytotoxic action by the intracellular inhibition of ribonucleases by RI [25].
  • Using the same method, a homogeneous RI was also obtained from human hindbrain (brainstem and cerebellum) [26].
  • The assay is based on the capacity of angiogenin to bind placental ribonuclease inhibitor (PRI); it is less tedious and more versatile than existing procedures that measure blood vessel growth or cleavage of rRNA [27].
  • Ribonuclease inhibitor (RI) was purified about 1300-fold from human cerebrum (including a small portion of midbrain) by a combination of ammonium sulfate precipitation, ribonuclease A-Sepharose chromatography, and high-performance anion-exchange chromatography [26].

Associations of RNH1 with chemical compounds

  • Human placental RNase inhibitor (hRI), a leucine-rich repeat protein, binds the blood vessel-inducing protein human angiogenin (Ang) with extraordinary affinity (Ki <1 fM) [28].
  • These results indicate that PRI inhibition minimally involves the three residues critical for the activity of angiogenin--Lys-40, His-13, and His-114--and to a lesser extent its single tryptophan, Trp-89 [29].
  • Carboxymethylation of His-13 or His-114 with bromoacetate increases the Ki value 15-fold, and oxidation of Trp-89 by means of dimethyl sulfoxide and hydrochloric acid increases it 2.4-fold, suggesting that these residues also form part of the contact region with PRI [29].
  • Modification of PRI with iodoacetic acid, p-(hydroxymercuri)benzoate, and 5,5'-dithiobis(2-nitrobenzoic acid) reveals that at least 30 of the 32 cysteine residues of PRI are in the reduced form [30].
  • This analysis has localized the ribonuclease inhibitor gene to chromosome subband 11p15.5, distal to the IGF2 gene [31].

Physical interactions of RNH1

  • RNase inhibitor (RI) binds diverse proteins in the pancreatic RNase superfamily with extremely high avidity [21].
  • Simultaneous substitutions of three neighboring tryptophans (261, 263, and 318) on RI attenuate affinity even more dramatically (by 4900-fold), indicating that the interactions of this RI region also contribute a considerable amount of the binding energy for the EDN complex [21].
  • RNase 4 binds tightly to the intracellular RNase inhibitor, with a Kd of 4 x 10(-15) M [32].
  • Of the four fractions resulting from phosphocellulose column chromatography of the whole cell extract, only the fraction that contained the RNA polymerase II activity was needed to accurately transcribe these nucleoprotein complexes in the presence of human placental ribonuclease inhibitor [33].

Regulatory relationships of RNH1

  • Thus, these results confirm that PRI inhibits angiogenin more effectively than RNase A [2].

Other interactions of RNH1

  • Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI) [34].
  • Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI [34].
  • The K(i) value for ANG with the deletion variant is 1.1 fM, only 2-fold higher than with WT RI [35].
  • The Crithidia fasciculata RNH1 gene encodes an RNase H, an enzyme that specifically degrades the RNA strand of RNA-DNA hybrids [22].
  • Despite the homology of ECP with certain RNases, placental RNasin, an RNase inhibitor, was unable to inhibit ECP-mediated toxicity [36].

Analytical, diagnostic and therapeutic context of RNH1

  • The rate constant for dissociation of the complex, determined by HPLC measurement of the rate of release of PR from its complex with PRI in the presence of a scavenger for free PRI, is 1.8 X 10(-7) s-1 [37].
  • Northern blot analysis revealed that the length of the RAI mRNA is approximately 1.9 kb [23].
  • The human RNH gene has been regionally localized to chromosome band 11p15 by in situ hybridization [38].
  • The purified RI appeared to be homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) [26].
  • 0. Two 25-kDa and 18-kDa RNases, which were obtained from human liver using a cellulose phosphate column, were bound to the immobilized RNase inhibitor and recovered in a pure and active form after treatment of the resin with p-hydroxymercuribenzoate [39].


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  22. The Crithidia fasciculata RNH1 gene encodes both nuclear and mitochondrial isoforms of RNase H. Engel, M.L., Hines, J.C., Ray, D.S. Nucleic Acids Res. (2001) [Pubmed]
  23. The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module. Schneider, R., Schneider-Scherzer, E., Thurnher, M., Auer, B., Schweiger, M. EMBO J. (1988) [Pubmed]
  24. 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]
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