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The X-chromosome linked intellectual disability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules

Item Type:Article
Title:The X-chromosome linked intellectual disability protein PQBP1 is a component of neuronal RNA granules and regulates the appearance of stress granules
Creators Name:Kunde, S.A. and Musante, L. and Grimme, A. and Fischer, U. and Mueller, E. and Wanker, E.E. and Kalscheuer, V.M.
Abstract:The polyglutamine-binding protein 1 (PQBP1) has been linked to several X-linked intellectual disability disorders and progressive neurodegenerative diseases. While it is currently known that PQBP1 localises in nuclear speckles and is engaged in transcription and splicing, we have now identified a cytoplasmic pool of PQBP1. Analysis of PQBP1 complexes revealed six novel interacting proteins, namely the RNA-binding proteins KSRP, SFPQ/PSF, DDX1 and Caprin-1, and two subunits of the intracellular transport related dynactin complex, p150(Glued) and p27. PQBP1 protein complex formation is dependent on the presence of RNA. Immunofluorescence studies revealed that in primary neurons PQBP1 colocalises with its interaction partners in specific cytoplasmic granules, which stained positive for RNA. Our results suggest that PQBP1 plays a role in cytoplasmic mRNA metabolism. This is further supported by the partial colocalisation and interaction of PQBP1 with the Fragile X mental retardation protein FMRP, which is one of the best-studied proteins found in RNA granules. In further studies, we show that arsenite-induced oxidative stress caused relocalisation of PQBP1 to stress granules (SGs), where PQBP1 colocalises with the new binding partners as well as with FMRP. Additional results indicated that the cellular distribution of PQBP1 plays a role in SG assembly. Together these data demonstrate a role for PQBP1 in the modulation of SGs and suggest its involvement in the transport of neuronal RNA granules, which are of critical importance for the development and maintenance of neuronal networks, thus illuminating a route by which PQBP1 aberrations might influence cognitive function.
Keywords:Biological Models, Cultured Cells, Cytoplasmic Granules, Fragile X Mental Retardation Protein, Intellectual Disability, Microtubule-Associated Proteins, Neurons, Oligopeptides, Protein Binding, Protein Transport, Ribosomes, RNA, RNA-Binding Proteins, X Human Chromosomes, X-Linked Genes, Animals, Mice
Source:Human Molecular Genetics
ISSN:0964-6906
Publisher:Oxford University Press (U.K.)
Volume:20
Number:24
Page Range:4916-4931
Date:15 December 2011
Official Publication:https://doi.org/10.1093/hmg/ddr430
PubMed:View item in PubMed

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