Abstract
In marmoset T cells transformed by Herpesvirus saimiri (HVS), a viral U-rich noncoding (nc) RNA, HSUR 1, specifically mediates degradation of host microRNA-27 (miR-27). High-throughput sequencing of RNA after crosslinking immunoprecipitation (HITS-CLIP) identified mRNAs targeted by miR-27 as enriched in the T cell receptor (TCR) signaling pathway, including GRB2. Accordingly, transfection of miR-27 into human T cells attenuates TCR-induced activation of mitogen-activated protein kinases (MAPKs) and induction of CD69. MiR-27 also robustly regulates SEMA7A and IFN-γ, key modulators and effectors of T cell function. Knockdown or ectopic expression of HSUR 1 alters levels of these proteins in virally transformed cells. Two other T-lymphotropic γ-herpesviruses, AlHV-1 and OvHV-2, do not produce a noncoding RNA to downregulate miR-27 but instead encode homologs of miR-27 target genes. Thus, oncogenic γ-herpesviruses have evolved diverse strategies to converge on common targets in host T cells.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Base Sequence
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Callithrix
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Enzyme Activation
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / metabolism
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GRB2 Adaptor Protein / genetics
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GRB2 Adaptor Protein / metabolism
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Gene Expression Regulation
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HEK293 Cells
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Herpesvirus 2, Saimiriine / genetics
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Herpesvirus 2, Saimiriine / metabolism*
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Herpesvirus 2, Saimiriine / pathogenicity
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High-Throughput Nucleotide Sequencing
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Host-Pathogen Interactions
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Humans
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Immunoprecipitation
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Jurkat Cells
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Lectins, C-Type / metabolism
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Lymphocyte Activation*
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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RNA Stability
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism*
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RNA, Viral / genetics
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RNA, Viral / metabolism*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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Semaphorins / genetics
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Semaphorins / metabolism
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Sequence Analysis, RNA
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / virology
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Time Factors
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Transfection
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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GPI-Linked Proteins
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GRB2 Adaptor Protein
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GRB2 protein, human
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IFNG protein, human
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Lectins, C-Type
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MIRN27 microRNA, human
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MicroRNAs
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RNA, Untranslated
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RNA, Viral
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Receptors, Antigen, T-Cell
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SEMA7A protein, human
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Semaphorins
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Interferon-gamma
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Mitogen-Activated Protein Kinases