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Gene Review

SNORD46  -  small nucleolar RNA, C/D box 46

Homo sapiens

Synonyms: RNU40, RNU46, U40, U46
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Disease relevance of SNORD46

  • Metal ion-induced changes in HIV-1 TAR RNA internal dynamics were determined by the changes in EPR spectral width for TAR RNAs containing spin-labeled nucleotides (U23, U25, U38, and U40) [1].
  • Eight healthy volunteers received on different study days s.c. injection of insulin aspart and U40 insulin (0.2 U/kg body weight) under euglycaemic clamp conditions (blood glucose 5 mmol/l, basal i.v. insulin infusion 0.15 mU/kg/min) [2].

High impact information on SNORD46

  • The TXA(2)-analog U46 619 and free arachidonate, but not PGI(2) or 12-HETE, induced increases in cytosolic Ca(++) and promoted phosphatidylserine (PS) exposure on a subpopulation of erythrocytes [3].
  • In conclusion, the lower insulin concentration of U40-insulin, higher skin temperature, and a thinner subcutaneous fat tissue at the injection site are associated with accelerated and enhanced subcutaneous insulin absorption [4].
  • Subcutaneous insulin absorption kinetics were assessed in 50 healthy study subjects (21 female, 29 male; age 26 +/- 3 years, BMI 22.5 +/- 1.8 kg/m2; mean +/- SD) during 45 min after periumbilical injection of soluble human U40- or U100-insulin (0.15 IU/kg) [4].
  • Based on a novel H5(C5)NN experiment for probing hydrogen-mediated 2hJ(N,N) scalar couplings as well as measured RDCs, the TAR-ARG complex is stabilized by a U38-A27.U23 base-triple involving an A27.U23 reverse Hoogsteen hydrogen bond alignment as well as by a A22-U40 Watson-Crick base-pair at the junction of stem I [5].
  • We have identified nine additional members of this family, U32 to U40 [6].

Biological context of SNORD46

  • Synergistic effects of CuCl2 and U46 D Fluid were also detected on the induction of DNA repair measured by unscheduled DNA synthesis [7].
  • Pharmacokinetics and pharmacodynamics of subcutaneously administered U40 and U100 formulations of regular human insulin [8].
  • In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h) [9].
  • Synergistic effects of Cu(II) and dimethylammonium 2,4-dichlorophenoxyacetate (U46 D fluid) on PM2 DNA and mechanism of DNA damage [10].
  • Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)) [11].

Anatomical context of SNORD46

  • The antiserum U46 (Go alpha) could identify in lymphocytes of young subjects two polypeptides 68,000 and 41,000 M(r) [12].
  • The cytotoxicity of U46 D Fluid was tested in human fibroblasts after pretreatment with non-toxic or slightly toxic concentrations of CuCl2 [7].

Associations of SNORD46 with chemical compounds

  • TAR RNAs containing single nitroxide spin-labels in the 2'-position of U23, U25, U38, or U40 were incubated with compounds known to inhibit TAR-Tat complex formation [13].
  • While Li(+) and K(+) had little effect on TAR RNA internal dynamics, Na(+) unexpectedly had a dynamic signature that was similar to Ca(2+) and Sr(2+), with a decrease in mobility at U23 and U38, little or no change at U25, and an increase in mobility at U40 [1].
  • Mg(2+), Co(2+), Ni(2+), Zn(2+), and Ba(2+) had similar effects on U23, U38, and U40, but the mobility of U25 was markedly increased [1].
  • At the three time points when significantly different serum insulin concentrations occurred soon after insulin injection, glucose infusion rates were not significantly different between U40 and U100 [8].
  • Synergistic effects of U46 D fluid (dimethylammonium salt of 2,4-D) and CuCl2 on cytotoxicity and DNA repair in human fibroblasts [7].

Other interactions of SNORD46

  • U32 to U40 are fibrillarin-associated, devoid of a 5'-trimethyl-cap and display an exclusively nucleolar localization [6].

Analytical, diagnostic and therapeutic context of SNORD46

  • The cross-ligated product increased when the reaction temperature was decreased during the reaction from 37 degrees C to 4 degrees C. A two-stranded hairpin ribozyme, divided into two fragments between G45 and U46 in a hairpin loop, showed higher ligation activity than the nondivided ribozyme [14].
  • Subcutaneous injection of the insulin analogue insulin aspart leads to a faster onset and a shorter duration of action even in comparison to U40 insulin [2].
  • In three different diabetes centers the use of insulin at a strength of 40 IU/ml (U40) and 100 IU/ml (U100) in continuous subcutaneous insulin infusion (CSII) treatment of insulin dependent (Type I) diabetic patients was compared in a randomized cross-over design [15].
  • FINDINGS: The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)) [11].


  1. EPR spectroscopic analysis of TAR RNA-metal ion interactions. Edwards, T.E., Sigurdsson, S.T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  2. Comparison of the time-action profiles of U40- and U100-regular human insulin and the rapid-acting insulin analogue B28 Asp. Heinemann, L., Weyer, C., Rave, K., Stiefelhagen, O., Rauhaus, M., Heise, T. Exp. Clin. Endocrinol. Diabetes (1997) [Pubmed]
  3. Platelet-erythrocyte interactions enhance alpha(IIb)beta(3) integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo. Vallés, J., Santos, M.T., Aznar, J., Martínez, M., Moscardó, A., Piñón, M., Broekman, M.J., Marcus, A.J. Blood (2002) [Pubmed]
  4. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. Sindelka, G., Heinemann, L., Berger, M., Frenck, W., Chantelau, E. Diabetologia (1994) [Pubmed]
  5. Argininamide binding arrests global motions in HIV-1 TAR RNA: comparison with Mg2+-induced conformational stabilization. Pitt, S.W., Majumdar, A., Serganov, A., Patel, D.J., Al-Hashimi, H.M. J. Mol. Biol. (2004) [Pubmed]
  6. Intron-encoded, antisense small nucleolar RNAs: the characterization of nine novel species points to their direct role as guides for the 2'-O-ribose methylation of rRNAs. Nicoloso, M., Qu, L.H., Michot, B., Bachellerie, J.P. J. Mol. Biol. (1996) [Pubmed]
  7. Synergistic effects of U46 D fluid (dimethylammonium salt of 2,4-D) and CuCl2 on cytotoxicity and DNA repair in human fibroblasts. Jacobi, H., Witte, I. Toxicol. Lett. (1991) [Pubmed]
  8. Pharmacokinetics and pharmacodynamics of subcutaneously administered U40 and U100 formulations of regular human insulin. Heinemann, L., Chantelau, E.A., Starke, A.A. Diabète & métabolisme. (1992) [Pubmed]
  9. The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection. Hübinger, A., Weber, W., Jung, W., Wehmeyer, K., Gries, F.A. The Clinical investigator. (1992) [Pubmed]
  10. Synergistic effects of Cu(II) and dimethylammonium 2,4-dichlorophenoxyacetate (U46 D fluid) on PM2 DNA and mechanism of DNA damage. Jacobi, H., Metzger, J., Witte, I. Free Radic. Res. Commun. (1992) [Pubmed]
  11. Therapeutic use of the natriuretic peptide ularitide in acute renal failure. Meyer, M., Pfarr, E., Schirmer, G., Uberbacher, H.J., Schöpe, K., Böhm, E., Flüge, T., Mentz, P., Scigalla, P., Forssmann, W.G. Renal failure. (1999) [Pubmed]
  12. Age-dependent changes in transmembrane signalling: identification of G proteins in human lymphocytes and polymorphonuclear leukocytes. Fulop, T., Barabas, G., Varga, Z., József, C., Csabina, S., Szucs, S., Seres, I., Szikszay, E., Jeney, Z., Penyige, A. Cell. Signal. (1993) [Pubmed]
  13. Electron paramagnetic resonance dynamic signatures of TAR RNA-small molecule complexes provide insight into RNA structure and recognition. Edwards, T.E., Sigurdsson, S.T. Biochemistry (2002) [Pubmed]
  14. Cross-ligation and exchange reactions catalyzed by hairpin ribozymes. Komatsu, Y., Koizumi, M., Sekiguchi, A., Ohtsuka, E. Nucleic Acids Res. (1993) [Pubmed]
  15. Clinical outcome of using insulin at 40 IU/ml and 100 IU/ml in pump treatment. Results of a controlled multi-center trial. Christiansen, J.S., Sonnenberg, G.E., Kverneland, A., Schmitz, A., Christensen, C.K., Hermansen, K., Ritzenhoff, A., Spraul, M., Loerup, B., Mogensen, C.E. Acta medica Scandinavica. (1987) [Pubmed]
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