Single-stranded microRNA mimics

RNA. 2012 Oct;18(10):1796-804. doi: 10.1261/rna.031278.111. Epub 2012 Aug 21.


miRNAs are ∼22-nt RNAs that bind to the Argonaute family of proteins and have important regulatory roles in plants and animals. Here, we show that miRNAs exhibit targeting activity in cells when delivered as single strands that are 5'-phosphorylated and that contain 2'-fluoro ribose modifications. Length preferences, chemical modification sensitivity, and genome-wide seed-based targeting all suggest that this activity is Ago-based. Activity could be enhanced by annealing of segmented passenger strands containing non-nucleic acid spacers. Furthermore, screening of randomly generated sequences identified pyrimidine rich 3' cassette sequences that increased single strand activity. These results provide an initial step in the development of single-stranded miRNA mimics for therapeutic use.

Publication types

  • Evaluation Study

MeSH terms

  • Base Sequence
  • Cloning, Molecular
  • DNA, Single-Stranded / chemical synthesis*
  • DNA, Single-Stranded / chemistry
  • Fluorides / chemical synthesis
  • Fluorides / chemistry
  • Gene Knockdown Techniques / instrumentation
  • Gene Knockdown Techniques / methods
  • HCT116 Cells
  • High-Throughput Screening Assays
  • Humans
  • MicroRNAs / chemistry*
  • Microarray Analysis
  • Molecular Mimicry* / physiology
  • Molecular Sequence Data
  • Phosphorylation
  • Ribose / chemical synthesis
  • Ribose / chemistry
  • Transfection


  • DNA, Single-Stranded
  • MicroRNAs
  • Ribose
  • Fluorides