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Mol Cell. 2014 Apr 10;54(1):67-79. doi: 10.1016/j.molcel.2014.03.025.

Alternative capture of noncoding RNAs or protein-coding genes by herpesviruses to alter host T cell function.

Author information

1
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536, USA.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
4
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.

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.

PMID:
24725595
PMCID:
PMC4039351
DOI:
10.1016/j.molcel.2014.03.025
[Indexed for MEDLINE]
Free PMC Article

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