Helmholtz Gemeinschaft


The Opitz syndrome gene product MID1 assembles a microtubule-associated ribonucleoprotein complex

Item Type:Article
Title:The Opitz syndrome gene product MID1 assembles a microtubule-associated ribonucleoprotein complex
Creators Name:Aranda-Orgilles, B. and Trockenbacher, A. and Winter, J. and Aigner, J. and Koehler, A. and Jastrzebska, E. and Stahl, J. and Mueller, E.C. and Otto, A. and Wanker, E.E. and Schneider, R. and Schweiger, S.
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 1alpha (EF-1alpha) 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-1alpha. 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.
Keywords:Annexin A2, Affinity Chromatography, Base Sequence, Cell Surface Receptors, Fluorescent Antibody Technique, GTP-Binding Proteins, HeLa Cells, Immunoprecipitation, In Situ Hybridization, Microtubule Proteins, Microtubules, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Nucleic Acid Sequence Homology, Peptide Elongation Factor 1, Ribonucleoproteins, RNA, Small Interfering RNA, Transcription Factors, Two-Hybrid System Techniques, X-Linked Genetic Diseases
Source:Human Genetics
Page Range:163-176
Date:March 2008
Official Publication:https://doi.org/10.1007/s00439-007-0456-6
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library