RNA-binding protein Dnd1 inhibits microRNA access to target mRNA

Cell. 2007 Dec 28;131(7):1273-86. doi: 10.1016/j.cell.2007.11.034.

Abstract

MicroRNAs (miRNAs) are inhibitors of gene expression capable of controlling processes in normal development and cancer. In mammals, miRNAs use a seed sequence of 6-8 nucleotides (nt) to associate with 3' untranslated regions (3'UTRs) of mRNAs and inhibit their expression. Intriguingly, occasionally not only the miRNA-targeting site but also sequences in its vicinity are highly conserved throughout evolution. We therefore hypothesized that conserved regions in mRNAs may serve as docking platforms for modulators of miRNA activity. Here we demonstrate that the expression of dead end 1 (Dnd1), an evolutionary conserved RNA-binding protein (RBP), counteracts the function of several miRNAs in human cells and in primordial germ cells of zebrafish by binding mRNAs and prohibiting miRNAs from associating with their target sites. These effects of Dnd1 are mediated through uridine-rich regions present in the miRNA-targeted mRNAs. Thus, our data unravel a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Conserved Sequence
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Silencing*
  • Germ Cells / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Regulatory Sequences, Ribonucleic Acid
  • Transcription, Genetic*
  • Transfection
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • Connexin 43
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Regulatory Sequences, Ribonucleic Acid
  • Zebrafish Proteins
  • nanos3 protein, zebrafish
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein-Serine-Threonine Kinases