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 Henrik 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.

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 Henrik Lund, Anastassis Perrakis, Erez Raz, Reuven Agami

531 Citations (Scopus)

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.
Udgivelsesdato: 2007-Dec-28

Original language	English
Journal	Cell
Volume	131
Issue number	7
Pages (from-to)	1273-86
Number of pages	13
ISSN	0092-8674
DOIs	https://doi.org/10.1016/j.cell.2007.11.034
Publication status	Published - 2007

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10.1016/j.cell.2007.11.034

Cite this

@article{b9126600046d11ddbee902004c4f4f50,

title = "RNA-binding protein Dnd1 inhibits microRNA access to target mRNA.",

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. Udgivelsesdato: 2007-Dec-28",

author = "Martijn Kedde and Strasser, {Markus J} and Bijan Boldajipour and Vrielink, {Joachim A F Oude} and Krasimir Slanchev and {le Sage}, Carlos and Remco Nagel and Voorhoeve, {P Mathijs} and {van Duijse}, Josyanne and {\O}rom, {Ulf Andersson} and Lund, {Anders Henrik} and Anastassis Perrakis and Erez Raz and Reuven Agami",

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

year = "2007",

doi = "10.1016/j.cell.2007.11.034",

language = "English",

volume = "131",

pages = "1273--86",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "7",

}

TY - JOUR

T1 - RNA-binding protein Dnd1 inhibits microRNA access to target mRNA.

AU - Kedde, Martijn

AU - Strasser, Markus J

AU - Boldajipour, Bijan

AU - Vrielink, Joachim A F Oude

AU - Slanchev, Krasimir

AU - le Sage, Carlos

AU - Nagel, Remco

AU - Voorhoeve, P Mathijs

AU - van Duijse, Josyanne

AU - Ørom, Ulf Andersson

AU - Lund, Anders Henrik

AU - Perrakis, Anastassis

AU - Raz, Erez

AU - Agami, Reuven

N1 - Keywords: 3' Untranslated Regions; Animals; Base Sequence; Binding Sites; Cell Line, Tumor; Connexin 43; Conserved Sequence; Cyclin-Dependent Kinase Inhibitor p27; Gene Expression Regulation, Developmental; Gene Silencing; Germ Cells; Humans; MicroRNAs; Molecular Sequence Data; Mutation; Protein Binding; Protein-Serine-Threonine Kinases; RNA, Messenger; RNA-Binding Proteins; Regulatory Sequences, Ribonucleic Acid; Transcription, Genetic; Transfection; Zebrafish; Zebrafish Proteins

PY - 2007

Y1 - 2007

N2 - 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. Udgivelsesdato: 2007-Dec-28

AB - 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. Udgivelsesdato: 2007-Dec-28

U2 - 10.1016/j.cell.2007.11.034

DO - 10.1016/j.cell.2007.11.034

M3 - Journal article

C2 - 18155131

SN - 0092-8674

VL - 131

SP - 1273

EP - 1286

JO - Cell

JF - Cell

IS - 7

ER -