Fluorometric determination of RNase H via a DNAzyme conjugated to reduced graphene oxide, and its application to screening for inhibitors and activators

Mikrochim Acta. 2019 May 7;186(6):335. doi: 10.1007/s00604-019-3425-6.

Abstract

A new fluorometric method is delineated for the detection of RNase H activity by combining DNAzyme with reduced graphene oxide (rGO). In the absence of RNase H, the fluorescence of FAM-labeled probe is quenched due to the strong adsorption on the rGO. The presence of RNase H can release the active DNAzyme from the DNA-RNA chimeric strand. This triggers the cleavage of the signal probe at the rA site with the help of the cofactor Mg2+. The recycle cleavage can directly result in the amplified signal emitted by the FAM-labeled short fragment. The method allows the activity of RNase H to be detected in a linear range of 0.01 to 5 U·mL-1. The detection limit of 0.018 U·mL-1 is calculated by the principle of three-time standard deviation over the blank signal. Then, RNase H-targeting natural compounds were screened for their inhibitory action. Among the investigated compounds, five were screened as RNase H inhibitors in a concentration-dependent manner, and 4 compounds were identified as activators. Finally, the method was reliably used for discriminating the difference of RNase H activity in human serum. It is found that RNase H activity was upregulated in patients with hepatitis C virus infection. Graphical abstract The schematic presentation of rGO-DNAzyme-based RNase H detection. RNase H triggers the active DNAzyme releasing from the DNA-RNA chimeric strand, which can cleavage probes to FAM-labeled short fragments and make the fluorescence signal cycle amplified.

Keywords: Concentration-dependent manner; Fluorescent probe; Hepatitis C virus; High sensitivity; Kinetic analysis; Model docking; Nanomaterial; Quenching efficiency; Signal amplification; Tumor cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Probes / chemistry*
  • DNA, Catalytic / chemistry*
  • Enzyme Inhibitors / chemistry
  • Fluoresceins / chemistry
  • Fluorescent Dyes / chemistry
  • Graphite / chemistry*
  • Humans
  • Limit of Detection
  • Ribonuclease H / antagonists & inhibitors
  • Ribonuclease H / blood*
  • Spectrometry, Fluorescence / methods*

Substances

  • DNA Probes
  • DNA, Catalytic
  • Enzyme Inhibitors
  • Fluoresceins
  • Fluorescent Dyes
  • graphene oxide
  • Graphite
  • Ribonuclease H