A novel function for fragile x mental retardation protein in translational activation.

Elias G. Bechara; Marie Cecile Didiot; Mireille Melko; Laetitia Davidovic; Mounia Bensaid; Patrick Martin; Marie Castets; Philippe Pognonec; Edouard W. Khandjian; Hervé Moine; Barbara Bardoni

inserm-00357398, version 1

A novel function for fragile x mental retardation protein in translational activation.
Bechara E. G., Didiot M. C., Melko M., Davidovic L., Bensaid M., Martin P., Castets M., Pognonec P., Khandjian E. W., Moine H. et al
PLoS Biology 7, 1 (2009) e16 - http://www.hal.inserm.fr/inserm-00357398

PMID: identifier of
Pubmed reference:

(19166269)

title:

A novel function for fragile x mental retardation protein in translational activation.

author(s):

Elias Bechara^{1, 2}, Marie Cecile Didiot², Mireille Melko¹, Laetitia Davidovic¹, Mounia Bensaid¹, Patrick Martin³, Marie Castets², Philippe Pognonec³, Edouard Khandjian⁴, Hervé Moine², Barbara Bardoni (

) ^{1, 2}

laboratory:

1:	IPMC - Institut de pharmacologie moléculaire et cellulaire

http://www.ipmc.cnrs.fr/

CNRS : UMR6097 – Université Nice Sophia Antipolis [UNS]

CNRS-IPMC 660 Route des lucioles 06560 VALBONNE

France

2:	IGBMC - Institut de génétique et biologie moléculaire et cellulaire

http://www-ulp.u-strasbg.fr/unite_recherche.php?u=14

CNRS : UMR7104 – INSERM : U596 – Université Louis Pasteur - Strasbourg I

I.G.B.M.C, Parc D'Innovation 1 Rue Laurent Fries - BP 10142 67404 ILLKIRCH CEDEX

France

3:	LBPSI - Biologie et physiopathologie des systèmes intégrés

http://www.unice.fr/FRE3094

CNRS : FRE3094 – Université Nice Sophia Antipolis [UNS]

bat. sciences nat 3, 6, 7éme niv Parc Valrose 06108 NICE CEDEX 2

France

4:	Neurobiologie Cellulaire

Université Laval

Centre de Recherche Robert Giffard Québec

Canada

abstract:

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet and the "kissing complex," which both induce translational repression in the presence of FMRP. We show here a new role for FMRP as a positive modulator of translation. FMRP specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is folded as three independent stem-loop structures. FMRP induces a structural modification of the SoSLIP motif upon its interaction with it. SoSLIP also behaves as a translational activator whose action is potentiated by the interaction with FMRP. The absence of FMRP results in decreased expression of Sod1. Because it has been observed that brain metabolism of FMR1 null mice is more sensitive to oxidative stress, we propose that the deregulation of Sod1 expression may be at the basis of several traits of the physiopathology of the Fragile X syndrome, such as anxiety, sleep troubles, and autism.

subject:

Life Sciences/Genetics

fulltext language:

English

ISSN:

1544-9173

publication format:

Article in peer-reviewed journal

DOI:

10.1371/journal.pbio.1000016

journal:

PLoS Biology (PLoS Biol)
Publisher	Public Library of Science
ISSN	1544-9173 (eISSN : 1545-7885)

Audience:

international

publication date:

2009-01-20

volume:

issue:

page, identifiant, ...:

e16

Attached file list to this document:

PDF

10.1371_journal.pbio.1000016-L.pdf

(3.7 MB)


inserm-00357398, version 1
http://www.hal.inserm.fr/inserm-00357398
oai:www.hal.inserm.fr:inserm-00357398
From: Maité Peney <>
Submitted on: Friday, 13 March 2009 16:48:03
Updated on: Friday, 13 March 2009 16:49:18