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RIBONOMIC ANALYSIS OF HUMAN DZIP1 REVEALS ITS INVOLVEMENT IN RIBONUCLEOPROTEIN COMPLEXES AND STRESS GRANULES
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Instituto de Investigaciones Biológicas Clemente Estable. Genomics Department. Montevideo, Uruguay. / Universidad de la República Uruguay. Facultad de Ciencias. Departamento de Biología Celular y Molecular. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Instituto Pasteur. Montevideo, Uruguay. / Universidad de la República Uruguay. Facultad de Ciencias. Departamento de Biología Celular y Molecular. Montevideo, Uruguay.
Instituto Pasteur. Montevideo, Uruguay.
National Laboratory for Cancer Research. Leidos Biomedical Research, Inc. Cancer Research Technology Program. Frederick, USA.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Instituto de Investigaciones Biológicas Clemente Estable. Genomics Department. Montevideo, Uruguay. / Universidad de la República Uruguay. Facultad de Ciencias. Departamento de Biología Celular y Molecular. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Instituto Pasteur. Montevideo, Uruguay. / Universidad de la República Uruguay. Facultad de Ciencias. Departamento de Biología Celular y Molecular. Montevideo, Uruguay.
Instituto Pasteur. Montevideo, Uruguay.
National Laboratory for Cancer Research. Leidos Biomedical Research, Inc. Cancer Research Technology Program. Frederick, USA.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Básica de Células Tronco. Curitiba, PR, Brasil.
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.
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