Molecular Properties, Functional Mechanisms, and Applications of Sliced siRNA

Guihua Sun, Spencer Yele Yeh, Christine Wan Yin Yuan, Margaret Jean Yih Chiu, Bryan Shing Hei Yung, Yun Yen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Using pre-miR-451 as a model molecule, we have characterized the general molecular properties of small hairpin RNAs that are processed into potent small interfering RNAs (siRNA) by Argonaute2 (Ago2). The Ago2-sliced siRNAs (sli-siRNAs) have the same silencing potency as the classical Dicer diced siRNAs (di-siRNAs) but have dramatically reduced unwanted sense strand activities. We have built vectors with the constitutive or inducible U6 promoter that can express sli-siRNAs in mammalian cells, in which the sli-siRNAs can be correctly processed to repress target genes. As a proof of principle for potential applications of sli-siRNAs in vivo, we show that the expression of one Ago2 shRNA-1148 in HCT-116 colon cancer cells knocked down RRM2 expression and reduced the proliferation and invasiveness of the cells. The defined sli-siRNA model molecules and the expression systems established in this study will facilitate the design and application of sli-siRNAs as novel potent RNAi triggers with reduced off-target effects.

Original languageEnglish
Article numbere221
Pages (from-to)e221
JournalMolecular Therapy - Nucleic Acids
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 27 2015
Externally publishedYes

Keywords

  • Ago2
  • agshRNA
  • agsiRNA
  • RNAi
  • siRNA
  • sliced siRNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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