Direct fluorescence detection of RNA on microarrays by surface-initiated enzymatic polymerization

Anal Chem. 2013 Jan 2;85(1):426-33. doi: 10.1021/ac303132j. Epub 2012 Dec 10.

Abstract

We report the first demonstration of surface-initiated enzymatic polymerization (SIEP) for the direct detection of RNA in a fluorescence microarray format. This new method incorporates multiple fluorophores into an RNA strand using the two-step sequential and complementary reactions catalyzed by yeast poly(A) polymerase (PaP) to incorporate deoxyadenosine triphosphate (dATP) at the 3'-OH of an RNA molecule, followed by terminal deoxynucleotidyl transferase (TdT) to catalyze the sequential addition of a mixture of natural and fluorescent deoxynucleotides (dNTPs) at the 3'-OH of an RNA-DNA hybrid. We found that the 3'-end of RNA can be efficiently converted into DNA (∼50% conversion) by polymerization of dATP using yeast PaP, and the short DNA strand appended to the end of the RNA by PaP acts as the initiator for the TdT-catalyzed polymerization of longer DNA strands from a mixture of natural and fluorescent dNTPs that contain up to ∼45 Cy3 fluorophores per 1 kb DNA. We obtained an ∼2 pM limit of detection (LOD) and a 3 log-linear dynamic range for hybridization of a short 21 base-long RNA target to an immobilized peptide nucleic acid probe, while fragmented mRNA targets from three different full length mRNA transcripts yielded a ∼10 pM LOD with a similar dynamic range in a microarray format.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carbocyanines / chemistry
  • Exoribonucleases / metabolism*
  • Fluorescent Dyes / chemistry*
  • Nucleic Acid Amplification Techniques*
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis*
  • Polymerization
  • RNA / analysis*
  • RNA / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Surface Properties

Substances

  • Carbocyanines
  • Fluorescent Dyes
  • cyanine dye 3
  • RNA
  • Exoribonucleases
  • poly(A)-specific ribonuclease