High-dose siRNAs upregulate mouse Eri-1 at both transcription and posttranscription levels

PLoS One. 2011;6(10):e26466. doi: 10.1371/journal.pone.0026466. Epub 2011 Oct 19.

Abstract

The eri-1 gene encodes a 3' exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri-1 by hd-siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Blotting, Western
  • CHO Cells
  • Chromatin Immunoprecipitation
  • Cricetinae
  • Cricetulus
  • DNA Primers
  • Electrophoretic Mobility Shift Assay
  • Exonucleases / genetics
  • Exonucleases / metabolism*
  • Exoribonucleases
  • Mice
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational*
  • RNA Interference
  • RNA Processing, Post-Transcriptional*
  • RNA, Small Interfering / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / physiology
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • DNA Primers
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Eri1 protein, mouse
  • Exonucleases
  • Exoribonucleases