RNA-binding protein Dnd1 inhibits microRNA access to target mRNA

Martijn Kedde; Markus J Strasser; Bijan Boldajipour; Joachim A F Oude Vrielink; Krasimir Slanchev; Carlos le Sage; Remco Nagel; P Mathijs Voorhoeve; Josyanne van Duijse; Ulf Andersson Ørom; Anders H Lund; Anastassis Perrakis; Erez Raz; Reuven Agami

doi:10.1016/j.cell.2007.11.034

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.

Authors

Martijn Kedde¹, Markus J Strasser, Bijan Boldajipour, Joachim A F Oude Vrielink, Krasimir Slanchev, Carlos le Sage, Remco Nagel, P Mathijs Voorhoeve, Josyanne van Duijse, Ulf Andersson Ørom, Anders H Lund, Anastassis Perrakis, Erez Raz, Reuven Agami

Affiliation

¹ The Netherlands Cancer Institute, Division of Tumor Biology, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.

PMID: 18155131
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