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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents



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ID: 407082.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
The Opitz syndrome gene product MID1 assembles a microtubule-associated ribonucleoprotein complex
Authors:Aranda-Orgillés, Beatriz; Trockenbacher, Alexander; Winter, Jennifer; Aigner, Johanna; Köhler, Andrea; Jastrzebska, Ewa; Stahl, Joachim; Müller, Eva-Christina; Otto, Albrecht; Wanker, Erich E.; Schneider, Rainer; Schweiger, Susann
Language:English
Date of Publication (YYYY-MM-DD):2008-01-03
Title of Journal:Human Genetics
Journal Abbrev.:Hum Gen
Volume:123
Issue / Number:2
Start Page:163
End Page:176
Copyright:© Springer. Part of Springer Science+Business Media
Review Status:not specified
Audience:Experts Only
Abstract / Description:Abstract Opitz BBB/G syndrome (OS) is a heterogenous malformation syndrome mainly characterised by hypertelorism and hypospadias. In addition, patients may present with several other defects of the ventral midline such as cleft lip and palate and congenital heart defects. The syndrome-causing gene encodes the X-linked E3 ubiquitin ligase MID1 that mediates ubiquitin-specific modification and degradation of the catalytic subunit of the translation regulator protein phosphatase 2A (PP2A). Here, we show that the MID1 protein also associates with elongation factor 1α (EF-1α) and several other proteins involved in mRNA transport and translation, including RACK1, Annexin A2, Nucleophosmin and proteins of the small ribosomal subunits. Mutant MID1 proteins as found in OS patients lose the ability to interact with EF-1α. The composition of the MID1 protein complex was determined by several independent methods: (1) yeast two-hybrid screening and (2) immunofluorescence, (3) a biochemical approach involving affinity purification of the complex, (4) co-fractionation in a microtubule assembly assay and (5) immunoprecipitation. Moreover, we show that the cytoskeleton-bound MID1/translation factor complex specifically associates with G- and U-rich RNAs and incorporates MID1 mRNA, thus forming a microtubule-associated ribonucleoprotein (RNP) complex. Our data suggest a novel function of the OS gene product in directing translational control to the cytoskeleton. The dysfunction of this mechanism would lead to malfunction of microtubule-associated protein translation and to the development of OS.
Electronic supplementary material The online version of this article (doi:10.1007/s00439-007-0456-6) contains supplementary material, which is available to authorized users.
Comment of the Author/Creator:Beatriz Aranda-Orgillés
Email: aranda@molgen.mpg.de

Contact Information: Rainer Schneider
(Corresponding author)
Email: rainer.schneider@uibk.ac.at
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Department of Biology, Chemistry and Pharmacy, Free University Berlin, Thielallee 63, 14195 Berlin, Germany;
2.Institute of Biochemistry, Center for Molecular Biosciences Innsbruck (CMBI), University Innsbruck, Peter-Mayr-Str. 1a, 6020 Innsbruck, Austria;
3.Department of Dermatology, Charité, Schumannstr. 21-22, 10117 Berlin, Germany;
4.Max-Delbrueck Center of Molecular Medicine, Robert-Roessle-Str. 10, 13125 Berlin, Germany;
5.Medical School, Division of Pathology and Neuroscience, University of Dundee, DD1 9SY Dundee, UK.
Identifiers:URL:http://www.springerlink.com/content/a650w111885653...
DOI:10.1007/s00439-007-0456-6
ISSN:0340-6717
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