| Absence of DICER in monocytes and its regulation by HIV-1. | |
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MedLine Citation:
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PMID: 20584909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's miRNA pathway for its own benefit. In this study, we examined the state of miRNA production in monocytes and macrophages as well as the consequences of viral infection upon the production of miRNA. Monocytes in general express low amounts of miRNA-related proteins, and DICER in particular could not be detected until after monocytes were differentiated into macrophages. In the case where HIV-1 was present prior to differentiation, the expression of DICER was suppressed. MicroRNA chip results for RNA isolated from transfected and treated cells indicated that a drop in miRNA production coincided with DICER protein suppression in macrophages. We found that the expression of DICER in monocytes is restricted by miR-106a, but HIV-1 suppressed DICER expression via the viral gene Vpr. Additionally, analysis of miRNA expression in monocytes and macrophages revealed evidence that some miRNAs can be processed by both DICER and PIWIL4. Results presented here have implications for both the pathology of viral infections in macrophages and the biogenesis of miRNAs. First, HIV-1 suppresses the expression and function of DICER in macrophages via a previously unknown mechanism. Second, the presence of miRNAs in monocytes lacking DICER indicates that some miRNAs can be generated by proteins other than DICER. |
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Authors:
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William Coley; Rachel Van Duyne; Lawrence Carpio; Irene Guendel; Kylene Kehn-Hall; Sebastien Chevalier; Aarthi Narayanan; Truong Luu; Norman Lee; Zachary Klase; Fatah Kashanchi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-11 Completed Date: 2010-12-07 Revised Date: 2011-11-03 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 31930-43 Citation Subset: IM |
Affiliation:
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National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation
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genetics Cell Line Eukaryotic Initiation Factor-2 / genetics, metabolism Eukaryotic Initiation Factors / genetics, metabolism Gene Expression Regulation Gene Knockdown Techniques HIV-1 / metabolism* Humans MicroRNAs / genetics, metabolism* Monocytes / cytology, enzymology*, physiology Oligonucleotide Array Sequence Analysis Proteins / genetics, metabolism Ribonuclease III / genetics, metabolism* vpr Gene Products, Human Immunodeficiency Virus / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI043894/AI/NIAID NIH HHS; AI074410/AI/NIAID NIH HHS; AI078859/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/EIF2C1 protein, human; 0/EIF2C2 protein, human; 0/Eukaryotic Initiation Factor-2; 0/Eukaryotic Initiation Factors; 0/MicroRNAs; 0/PIWIL4 protein, human; 0/Proteins; 0/vpr Gene Products, Human Immunodeficiency Virus; 0/vpr protein, Human immunodeficiency virus 1; EC 3.1.26.3/DROSHA protein, human; EC 3.1.26.3/Ribonuclease III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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