title: The effects of siRNA-mediated RGS4 gene silencing on the whole genome transcription profile: implications for schizophrenia.
abstract: OBJECTIVE
  The regulator of G-protein signaling (RGS) molecules represent a class of proteins that modulate the signaling activity of G-protein coupled receptors. Regulator of G-protein signaling 4 (RGS4) is of particular interest in schizophrenia due to reported downregulation of RGS4 transcripts in schizophrenia as well as a connection between RGS4 and a number of receptors implicated in schizophrenia. The mechanism of RGS4 involvement in the pathophysiology of this illness is not clear.
  
  
  METHODS
  To elucidate thise role of RGS4 in pathophysiology of schizophrenia, we silenced RGS4 using siRNAs in human neuroblastoma cell lines and we studied the effects of differential RGS4 expression by microarray.
  
  
  CONCLUSIONS
  The cell lines with downregulated expression of RGS4 showed 67 genes with changed expression (30 underexpressed and 37 overexpressed). We have detected three subgroups of genes which might be implicated in schizophrenia pathophysiology: histone genes, which suggest epigenetic mechanisms of the disease; genes for transcription factors associated with other genes relevant to schizophrenia pathology (BDNF and DISCI1) and a heterogeneous group containing genes for G-proteins (GPR50 and GPR64) and calcium binding proteins.
authors.affiliation: Prague Psychiatric Centre, Czech Republic. vrajova@pcp.lf3.cuni.cz
authors.forename: Monika
authors.initials: M
authors.lastname: Vrajová
authors.forename: Soňa
authors.initials: S
authors.lastname: Peková
authors.forename: Jirí
authors.initials: J
authors.lastname: Horácek
authors.forename: Cyril
authors.initials: C
authors.lastname: Höschl
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015894:Genome, Human / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C105986:ADGRG2 protein, human; D019208:Brain-Derived Neurotrophic Factor; C509754:GPR50 protein, human; D006657:Histones; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C098799:RGS4 protein