Dicer-independent processing of small RNA duplexes: mechanistic insights and applications

Nucleic Acids Res. 2017 Oct 13;45(18):10369-10379. doi: 10.1093/nar/gkx779.

Abstract

MicroRNAs (miRNAs) play a pivotal role in the regulation of cellular gene expression via the conserved RNA interference (RNAi) mechanism. Biogenesis of the unusual miR-451 does not require Dicer. This molecule is instead processed by the Argonaute 2 (Ago2) enzyme. Similarly, unconventional short hairpin RNA (shRNA) molecules have been designed as miR-451 mimics that rely exclusively on Ago2 for maturation. We will review recent progress made in the understanding of this alternative processing route. Next, we describe different Dicer-independent shRNA designs that have been developed and discuss their therapeutic advantages and disadvantages. As an example, we will present the route towards development of a durable gene therapy against HIV-1.

Publication types

  • Review

MeSH terms

  • Animals
  • DEAD-box RNA Helicases / physiology*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / metabolism*
  • Nucleic Acid Conformation
  • RNA Interference / physiology
  • RNA Processing, Post-Transcriptional*
  • RNA, Double-Stranded / metabolism*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / metabolism
  • Ribonuclease III / physiology*

Substances

  • MicroRNAs
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases