Visualization of single mRNAs reveals temporal association of proteins with microRNA-regulated mRNA

Nucleic Acids Res. 2011 Sep 1;39(17):7740-9. doi: 10.1093/nar/gkr456. Epub 2011 Jun 7.

Abstract

Although many proteins are known to function in microRNA (miRNA)-based translational repression, we lack a comprehensive understanding of temporal relationships between the mRNA, miRNA and their constituent proteins. To understand the dynamics of miRNA and protein interactions, we created a synthetic inducible miRNA system in mammalian cells. By visualizing single mRNAs and observing their co-localization with proteins over time, we produced a temporal association map of miRNA-associated factors. Argonaute2, Dcp1a, hedls and Rck co-localize with miRNA-regulated mRNA after 24 h of miRNA induction, and RNAi knockdown of any one of these proteins affected the co-localization of any of the other proteins with miRNA-regulated mRNA, demonstrating that these proteins could interact with each other in a complex. We identified Argonaute2 and hedls as proteins that co-localize and interact with miRNA-regulated mRNA, indicating that processing body components are involved in long-term storage of miRNA-regulated mRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Genes, Reporter
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / metabolism*
  • RNA Interference*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / metabolism*
  • RNA-Induced Silencing Complex / analysis
  • RNA-Induced Silencing Complex / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex