Argonaute 2-dependent regulation of gene expression by single-stranded miRNA mimics

Masayuki Matsui, Thazha P. Prakash, David R. Corey

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.

Original languageEnglish (US)
Pages (from-to)946-955
Number of pages10
JournalMolecular Therapy
Volume24
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Gene Expression Regulation
MicroRNAs
RNA Interference
Gene Silencing
Gene Expression
Argonaute Proteins
Double-Stranded RNA
Oligonucleotides
Pharmaceutical Preparations
Cell Culture Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Argonaute 2-dependent regulation of gene expression by single-stranded miRNA mimics. / Matsui, Masayuki; Prakash, Thazha P.; Corey, David R.

In: Molecular Therapy, Vol. 24, No. 5, 01.05.2016, p. 946-955.

Research output: Contribution to journalArticle

Matsui, Masayuki ; Prakash, Thazha P. ; Corey, David R. / Argonaute 2-dependent regulation of gene expression by single-stranded miRNA mimics. In: Molecular Therapy. 2016 ; Vol. 24, No. 5. pp. 946-955.
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