Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155

被引:339
作者
Skalsky, Rebecca L. [1 ]
Samols, Mark A. [1 ]
Plaisance, Karlie B. [1 ]
Boss, Isaac W. [1 ]
Riva, Alberto [1 ]
Lopez, M. Cecilia [1 ]
Baker, Henry V. [1 ]
Renne, Rolf [1 ]
机构
[1] Shands Canc Ctr, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
关键词
D O I
10.1128/JVI.01804-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression by binding to 3'-untranslated regions (3'UTRs) of target mRNAs. Kaposi's sarcoma-associated herpesvirus (KSHV), a virus linked to malignancies including primary effusion lymphoma (PEL), encodes 12 miRNA genes, but only a few regulatory targets are known. We found that KSRV-miR-K12-11 shares 100% seed sequence homology with hsa-miR-155, an miRNA frequently found to be up-regulated in lymphomas and critically important for B-cell development. Based on this seed sequence homology, we hypothesized that both miRNAs regulate a common set of target genes and, as a result, could have similar biological activities. Examination of five PEL lines showed that PELs do not express miR-155 but do express high levels of miR-K12-11. Bioinformatic tools predicted the transcriptional repressor BACH-1 to be targeted by both miRNAs, and ectopic expression of either miR-155 or miR-K12-11 inhibited a BACH-1 3'UTR-containing reporter. Furthermore, BACH-1 protein levels are low in cells expressing either miRNA. Gene expression profiling of miRNA-expressing stable cell lines revealed 66 genes that were commonly down-regulated. For select genes, miRNA targeting was confirmed by reporter assays. Thus, based on our in silico predictions, reporter assays, and expression profiling data, miR-K12-11 and miR-155 regulate a common set of cellular targets. Given the role of miR-155 during B-cell maturation, we speculate that miR-K12-11 may contribute to the distinct developmental phenotype of PEL cells, which are blocked in a late stage of B-cell development. Together, these findings indicate that KSHV miR-K12-11 is an ortholog of miR-155.
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页码:12836 / 12845
页数:10
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