Document Detail

RNA-binding protein QKI regulates Glial fibrillary acidic protein expression in human astrocytes.
MedLine Citation:
PMID:  23321059     Owner:  NLM     Status:  Publisher    
Linkage, association and expression studies previously pointed to the human QKI, KH domain containing, RNA-binding (QKI) as a candidate gene for schizophrenia. Functional studies of the mouse ortholog Qk focused mainly on its role in oligodendrocyte development and myelination, while its function in astroglia remained unexplored. Here we show that QKI is highly expressed in human primary astrocytes and that its splice forms encode proteins targeting different sub-cellular localizations. Uncovering the role of QKI in astrocytes is of interest in light of growing evidence implicating astrocyte dysfunction in the pathogenesis of several disorders of the central nervous system. We selectively silenced QKI splice variants in human primary astrocytes and used RNA sequencing to identify differential expression and splice variant composition at the genome-wide level. We found that mRNA expression of Glial fibrillary acidic protein (GFAP), encoding a major component of astrocyte intermediate filaments, was down-regulated after QKI7 splice variant silencing. Moreover, we identified a potential QKI binding site within the 3'untranslated region of human GFAP. This sequence was not conserved between mice and humans, raising the possibility that GFAP is a target for QKI in humans but not rodents. Haloperidol treatment of primary astrocytes resulted in coordinated increases in QKI7 and GFAP expression. Taken together, our results provide the first link between QKI and GFAP, two genes with alterations previously observed independently in schizophrenic patients. Our findings for QKI, together with its well-known role in myelination, suggest that QKI is a hub regulator of glia function in humans.
Katarzyna J Radomska; Jonatan Halvardson; Björn Reinius; Eva Lindholm Carlström; Lina Emilsson; Lars Feuk; Elena Jazin
Related Documents :
22480519 - Egcg inhibits tat-induced ltr transactivation: role of nrf2, akt, ampk signaling pathway.
12526889 - Axonal localization of delta ca2+/calmodulin-dependent protein kinase ii in developing ...
23272019 - Correction: broad expression analysis of human antxr1/tem8 transcripts reveals differen...
19513619 - Selection of optimal antisense accessible sites of uroplakin ii mrna for bladder urothe...
10817589 - Expression of angiotensin ii at2 receptor in the acute phase of stroke in rats.
19418629 - Mechanisms of angiotensin ii-mediated regulation of aldosterone synthase expression in ...
20194819 - Induction of tissue factor by urokinase in lung epithelial cells and in the lungs.
18718529 - Catabolite repression control of flagellum production by serratia marcescens.
17491019 - Specificity in beta cell expression of l-3-hydroxyacyl-coa dehydrogenase, short chain, ...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Human molecular genetics     Volume:  -     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Evolution and Development, Evolutionary Biology Centre, Uppsala University, 75235 Uppsala, Sweden.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Next Document:  Modulation of FGF receptor signaling as an intervention and potential therapy for myelin breakdown i...