Antibody-free photoelectrochemical strategy for simultaneous detection of methylated RNA, METTL3/METTL14 protein and MazF protein based on enhanced photoactivity of MoSe2-BiOI nanocomposite

Biosens Bioelectron. 2023 Feb 15:222:115015. doi: 10.1016/j.bios.2022.115015. Epub 2022 Dec 14.

Abstract

Taking advantages of the catalytic activity of METTL3/METTL14 protein towards adenine methylation in RNA sequence and the specific digestion activity of MazF protein towards unmethylated RNA sequence containing ACA bases, a novel photoelectrochemical biosensor was constructed for simultaneous detection of RNA methylation, METTL3/METTL14 protein and MazF protein. MoSe2-BiOI nanocomposite was prepared and considered as photoactive material, catalytic hairpin assembly strategy and in situ generation of electron donors catalyzed by polyaspartic acid-loaded alkaline phosphatase technique were employed as signal amplification. Under the optimum conditions, the detection ranges of methylated RNA, METTL3/METTL14 protein and MazF protein were 0.001-50 nM, 0.001-25 ng/μL, and 0.001-10 U/mL, respectively. The corresponding detection limits were 0.46 pM, 0.51 pg/μL and 0.42 U/μL with S/N = 3. In addition, the effect of drugs and composite pollutants on the activities of MazF proteins was assessed, proving the applicability of the developed method in the field of drug screening for MazF-related diseases. Moreover, the effects of pollutants on the activity of METTL3/METTL14 were also preliminarily explored, providing new information on pathogenic mechanism of pollutants.

Keywords: METTL3/METTL14; MazF; MoSe(2)–BiOI; N(6)-methyladenosine; Photoelectrochemical biosensor; RNA methylation.

MeSH terms

  • Adenosine
  • Antibodies / metabolism
  • Biosensing Techniques*
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • RNA* / genetics

Substances

  • RNA
  • Adenosine
  • Methyltransferases
  • Antibodies