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
-
- RNA, Messenger/metabolism*
- Humans
- Zebrafish
- Germ Cells/metabolism*
- Gene Silencing*
- Transfection
- 3' Untranslated Regions
- Regulatory Sequences, Ribonucleic Acid
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Molecular Sequence Data
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Connexin 43/genetics
- Connexin 43/metabolism
- Cell Line, Tumor
- Gene Expression Regulation, Developmental*
- MicroRNAs/metabolism*
- Cyclin-Dependent Kinase Inhibitor p27/genetics
- Cyclin-Dependent Kinase Inhibitor p27/metabolism
- Protein Binding
- Conserved Sequence
- Animals
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/metabolism
- Base Sequence
- Mutation
- Transcription, Genetic*
- Binding Sites
- PubMed
- 18155131 Full text @ Cell
Citation
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. (2007) RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA. Cell. 131(7):1273-1286.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping