title: Ribonomic analysis of human DZIP1 reveals its involvement in ribonucleoprotein complexes and stress granules.
abstract: BACKGROUND
  DZIP1 (DAZ-interacting protein 1) has been described as a component of the Hh signaling pathway with a putative regulatory role in ciliogenesis. DZIP1 interacts with DAZ RNA binding proteins in embryonic stem cells and human germ cells suggesting a role in mRNA regulation.
  
  
  RESULTS
  We investigated DZIP1 function in HeLa cells and its involvement in ribonucleoprotein complexes. DZIP1 was predominantly located in granules in the cytoplasm. Under oxidative stress conditions, DZIP1 re-localized to stress granules. DZIP appears to be important for the formation of stress granules during the stress response. We used immunoprecipitation assays with antibodies against DZIP1 and microarray hybridization to identify mRNAs associated with DZIP1. The genetic networks formed by the DZIP1-associated mRNAs were involved in cell cycle and gene expression regulation. DZIP1 is involved in the Hedgehog signaling pathway. We used cyclopamine, a specific inhibitor of this pathway, to analyze the expression of DZIP1 and its associated mRNAs. The abundance of DZIP1-associated mRNAs increased with treatment; however, the silencing or overexpression of DZIP1 in HeLa cells had no effect on the accumulation of the associated mRNAs. Polysomal profile analysis by sucrose gradient centrifugation demonstrated the presence of DZIP1 in the polysomal fraction.
  
  
  CONCLUSIONS
  Our results suggest that DZIP1 is part of an RNP complex that occupies various subcellular locations. The diversity of the mRNAs associated with DZIP1 suggests that this protein is a component of different RNPs associated with translating polysomes and with RNA granules.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Shigunov
authors.forename: Jose
authors.initials: J
authors.lastname: Sotelo-Silveira
authors.forename: Marco Augusto
authors.initials: MA
authors.lastname: Stimamiglio
authors.forename: Crisciele
authors.initials: C
authors.lastname: Kuligovski
authors.forename: Florencia
authors.initials: F
authors.lastname: Irigoín
authors.forename: Jose L
authors.initials: JL
authors.lastname: Badano
authors.forename: David
authors.initials: D
authors.lastname: Munroe
authors.forename: Alejandro
authors.initials: A
authors.lastname: Correa
authors.affiliation: Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas, FIOCRUZ, Algacyr Munhoz Mader 3775, Curitiba 81350-010, Brazil. brunod@tecpar.br.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallagiovanna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492524:DZIP1 protein, human; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins