RNA Interference-Mediated Gene Silencing by Branched Tripodal RNAs Does Not Require Dicer Processing

Nucleic Acid Ther. 2018 Feb;28(1):44-49. doi: 10.1089/nat.2017.0681. Epub 2017 Dec 1.

Abstract

Specific gene silencing through RNA interference (RNAi) holds great promise as the next-generation therapeutic development platform. Previously, we have shown that branched, tripodal interfering RNA (tiRNA) structures could simultaneously trigger RNAi-mediated gene silencing of three target genes with 38 nt-long guide strands associated with Argonaute 2. Herein, we show that the branched RNA structure can trigger effective gene silencing in Dicer knockout cell line, demonstrating that the Dicer-mediated processing is not required for tiRNA activity. The finding of this study confirms the flexibility of the structure of RNAi triggers as well as the length of the guide strand in RNAi-mediated gene silencing.

Keywords: Dicer; RNA interference; tripodal RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Base Sequence
  • Cell Line
  • DEAD-box RNA Helicases / deficiency
  • DEAD-box RNA Helicases / genetics*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Luciferases / antagonists & inhibitors
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Nucleic Acid Conformation
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA Interference*
  • RNA, Guide, CRISPR-Cas Systems
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Ribonuclease III / deficiency
  • Ribonuclease III / genetics*
  • Survivin / antagonists & inhibitors
  • Survivin / genetics
  • Survivin / metabolism
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • BIRC5 protein, human
  • CTNNB1 protein, human
  • MicroRNAs
  • RNA, Small Interfering
  • Survivin
  • beta Catenin
  • mirnlet7 microRNA, human
  • Luciferases
  • Proto-Oncogene Proteins c-met
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases