 embryo development. Interestingly, Prep1 contains a putative binding motif for 4EHP, which may reflect a novel unknown function. development effect. mRNA to the 5′ cap structure. This is the first demonstration that a mammalian homeodomain transcription factor regulates translation, and that this function can be possibly essential for the development of female germ cells and involved in mammalian zygote development

A Kuliev

AC Brun

AJ Waskiewicz

AM Thomson

AR Tee

B Oh

CB Moens

CL Chatot

Claudia Buratti

D Niessing

D Penkov

Dmitry Penkov

E Ferretti

E Rom

Elisabetta Ferretti

F Angenstein

F Gebauer

F Sedarat

Francesco Blasi

G Deflorian

I Topisirovic

J Berthelsen

J Huarte

J Zuberek

J. Carlos Villaescusa

JC Villaescusa

Jesús Planagumà

JL Semotok

K Chawengsaksophak

Lisa Mathiasen

M Stauber

Michael Polymenis

MT Murtha

P Di Rosa

PF Cho

R Bachvarova

RM Schultz

S Kuersten

S Niranjanakumari

S Ponsuksili

S Small

SV Costes

T Brend

VM Diaz

W Driever

PLoS ONE

English

PubMed

Crossref

Cytoplasmic Prep1 Interacts with 4EHP Inhibiting Hoxb4 Translation

BackgroundHomeobox genes are essential for embryonic patterning and cell fate determination. They are regulated mostly at the transcriptional level. In particular, Prep1 regulates Hox transcription in association with Pbx proteins. Despite its nuclear role as a transcription factor, Prep1 is located in the cytosol of mouse oocytes from primary to antral follicles. The homeodomain factor Bicoid (Bcd) has been shown to interact with 4EHP (eukaryotic translation initiation factor 4E homolog protein) to repress translation of Caudal mRNA and to drive Drosophila embryo development. Interestingly, Prep1 contains a putative binding motif for 4EHP, which may reflect a novel unknown function.Methodology/principal findingsIn this paper we show by confocal microscopy and deconvolution analysis that Prep1 and 4EHP co-localize in the cytosol of growing mouse oocytes, demonstrating their interaction by co-immunoprecipitation and pull-down experiments. A functional 4EHP-binding motif present in Prep1 has been also identified by mutagenesis analysis. Moreover, Prep1 inhibits (>95%) the in vitro translation of a luciferase reporter mRNA fused to the Hoxb4 3'UTR, in the presence of 4EHP. RNA electrophoretic mobility shift assay was used to demonstrate that Prep1 binds the Hoxb4 3'UTR. Furthermore, conventional histology and immunohistochemistry has shown a dramatic oocyte growth failure in hypomorphic mouse Prep1(i/i) females, accompanied by an increased production of Hoxb4. Finally, Hoxb4 overexpression in mouse zygotes showed a slow in vitro development effect.ConclusionsPrep1 has a novel cytoplasmic, 4EHP-dependent, function in the regulation of translation. Mechanistically, the Prep1-4EHP interaction might bridge the 3'UTR of Hoxb4 mRNA to the 5' cap structure. This is the first demonstration that a mammalian homeodomain transcription factor regulates translation, and that this function can be possibly essential for the development of female germ cells and involved in mammalian zygote development

J Carlos Villaescusa

Directory of Open Access Journals

Cytoplasmic Prep1 interacts with 4EHP inhibiting Hoxb4 translation.

Villaescusa J. Carlos

Buratti Claudia

Penkov Dmitry

Mathiasen Lisa

Planagumà Jesús

Ferretti Elisabetta

Blasi Francesco

Public Library of Science (PLOS)

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2664923

Cytoplasmic Prep1 Interacts with 4EHP Inhibiting Hoxb4 Translation

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Directory of Open Access Journals

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