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PMID: 16055709 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

ADAR1 interacts with NF90 through double-stranded RNA and regulates NF90-mediated gene expression independently of RNA editing.

Molecular and cellular biology ·Vol. 25 ·No. 16 ·2005-08-00 ·Pages 6956-63

Nie Y, Ding L, Kao PN, Braun R, Yang JH

Abstract

The RNA-editing enzyme ADAR1 modifies adenosines by deamination and produces A-to-I mutations in mRNA. ADAR1 was recently demonstrated to function in host defense and in embryonic erythropoiesis during fetal liver development. The mechanisms for these phenotypic effects are not yet known. Here we report a novel function of ADAR1 in the regulation of gene expression by interacting with the nuclear factor 90 (NF90) proteins, known regulators that bind the antigen response recognition element (ARRE-2) and have been demonstrated to stimulate transcription and translation. ADAR1 upregulates NF90-mediated gene expression by interacting with the NF90 proteins, including NF110, NF90, and NF45. A knockdown of NF90 with small interfering RNA suppresses this function of ADAR1. Coimmunoprecipitation and double-stranded RNA (dsRNA) digestion demonstrate that ADAR1 is associated with NF110, NF90, and NF45 through the bridge of cellular dsRNA. Studies with ADAR1 deletions demonstrate that the dsRNA binding domain and a region covering the Z-DNA binding domain and the nuclear export signal comprise the complete function of ADAR1 in upregulating NF90-mediated gene expression. These data suggest that ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins.

MeSH Terms
Adenosine Deaminase/metabolism,physiology Animals Cell Line Cell Line, Tumor Gene Expression Regulation Genes, Reporter Genetic Vectors Humans Immunoblotting Immunoprecipitation Luciferases/metabolism Mass Spectrometry Mice Nuclear Factor 90 Proteins Phosphoproteins/metabolism,physiology Polymerase Chain Reaction Protein Binding Protein Biosynthesis Protein Structure, Tertiary RNA Editing RNA, Double-Stranded/metabolism RNA, Messenger/metabolism RNA, Small Interfering/metabolism RNA-Binding Proteins/metabolism,physiology Response Elements Ribonucleases/metabolism Signal Transduction Transcription, Genetic Transfection Up-Regulation
Chemicals
ILF3 protein, human Nuclear Factor 90 Proteins Phosphoproteins RNA, Double-Stranded RNA, Messenger RNA, Small Interfering RNA-Binding Proteins Luciferases Ribonucleases ADARB1 protein, human Adenosine Deaminase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nie Yongzhan
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Ding Li
Kao Peter N
Braun Robert
Yang Jing-Hua
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.16.6956-6963.2005
Published
2005-08-00
Pages
6956-63
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1190226
Subset
IM
Grants
NIAID NIH HHS · K02 AI060701 · United States
NIGMS NIH HHS · R01 GM060426 · United States
NIAID NIH HHS · AI060701 · United States
NIGMS NIH HHS · GM-60426 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.16.6956-6963.2005 PMC Full Text View journal details
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