PUBLICATION

RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA

Authors
Kedde, M., Strasser, M.J., Boldajipour, B., Oude Vrielink, J.A., Slanchev, K., le Sage, C., Nagel, R., Voorhoeve, P.M., van Duijse, J., Andersson Ørom, U., Lund, A.H., Perrakis, A., Raz, E., and Agami, R.
ID
ZDB-PUB-071227-14
Date
2007
Source
Cell   131(7): 1273-1286 (Journal)
Registered Authors
Boldajipour, Bijan, Nagel, Roland, Raz, Erez, Slanchev, Krasimir, Strasser, Markus
Keywords
none
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*
PubMed
18155131 Full text @ Cell
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping