Relief of microRNA-mediated translational repression in human cells subjected to stress

Cell. 2006 Jun 16;125(6):1111-24. doi: 10.1016/j.cell.2006.04.031.


In metazoans, most microRNAs imperfectly base-pair with the 3' untranslated region (3'UTR) of target mRNAs and prevent protein accumulation by either repressing translation or inducing mRNA degradation. Examples of specific mRNAs undergoing microRNA-mediated repression are numerous, but whether the repression is a reversible process remains largely unknown. Here we show that cationic amino acid transporter 1 (CAT-1) mRNA and reporters bearing its 3'UTR can be relieved from the microRNA miR-122-induced inhibition in human hepatocarcinoma cells subjected to different stress conditions. The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes. The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA. We propose that proteins interacting with the 3'UTR will generally act as modifiers altering the potential of miRNAs to repress gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Amino Acids / deficiency
  • Antigens, Surface / metabolism
  • Arsenites / pharmacology
  • Cationic Amino Acid Transporter 1 / genetics
  • Cationic Amino Acid Transporter 1 / metabolism*
  • Cell Line, Tumor
  • Culture Media
  • Cytoplasmic Structures / metabolism
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Humans
  • MicroRNAs / physiology*
  • Oxidative Stress
  • Protein Binding
  • Protein Biosynthesis*
  • RNA Stability*
  • RNA Transport
  • RNA-Binding Proteins / metabolism
  • Sodium Compounds / pharmacology
  • Thapsigargin / pharmacology
  • Up-Regulation


  • 3' Untranslated Regions
  • Amino Acids
  • Antigens, Surface
  • Arsenites
  • Cationic Amino Acid Transporter 1
  • Culture Media
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • MicroRNAs
  • RNA-Binding Proteins
  • SLC7A1 protein, human
  • Sodium Compounds
  • sodium arsenite
  • Thapsigargin