MicroRNA-155 is an Epstein-Barr virus-induced gene that modulates Epstein-Barr virus-regulated gene expression pathways.
The cellular microRNA miR-155 has been shown to be involved in lymphocyte activation and is expressed in Epstein-Barr virus (EBV)-infected cells displaying type III latency gene expression but not type I latency gene expression. We show here that the elevated levels of miR-155 in type III latency cells is due to EBV gene expression and not epigenetic differences in cell lines tested, and we show that expression in EBV-infected cells requires a conserved AP-1 element in the miR-155 promoter. Gene expression analysis was carried out in a type I latency cell line transduced with an miR-155-expressing retrovirus. This analysis identified both miR-155-suppressed and -induced cellular mRNAs and suggested that in addition to direct targeting of 3' untranslated regions (UTRs), miR-155 alters gene expression in part through the alteration of signal transduction pathways. 3' UTR reporter analysis of predicted miR-155 target genes identified the transcriptional regulatory genes encoding BACH1, ZIC3, HIVEP2, CEBPB, ZNF652, ARID2, and SMAD5 as miR-155 targets. Western blot analysis of the most highly suppressed of these, BACH1, showed lower expression in cells transduced with a miR-155 retrovirus. Inspection of the promoters from genes regulated in EBV-infected cells and in cells infected with an miR-155 retrovirus identified potential binding sequences for BACH1 and ZIC3. Together, these experiments suggest that the induction of miR-155 by EBV contributes to EBV-mediated signaling in part through the modulation of transcriptional regulatory factors.
Yin
Qinyan
Q
Louisiana Cancer Research Consortium, New Orleans, USA.
McBride
Jane
J
Fewell
Claire
C
Lacey
Michelle
M
Wang
Xia
X
Lin
Zhen
Z
Cameron
Jennifer
J
Flemington
Erik K
EK
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D035683:MicroRNAs; D018808:Transcription Factor AP-1