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

Rebecca Skalsky, Mark A. Samols, Karlie B. Plaisance, Isaac W. Boss, Alberto Riva, M. Cecilia Lopez, Henry V. Baker, Rolf Renne

Research output: Contribution to journalArticle

357 Citations (Scopus)

Abstract

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 KSHV-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.

Original languageEnglish (US)
Pages (from-to)12836-12845
Number of pages10
JournalJournal of Virology
Volume81
Issue number23
DOIs
StatePublished - Dec 2007
Externally publishedYes

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Human herpesvirus 8
Human Herpesvirus 8
MicroRNAs
microRNA
Primary Effusion Lymphoma
lymphoma
B-lymphocytes
B-Lymphocytes
3' Untranslated Regions
3' untranslated regions
Sequence Homology
sequence homology
Seeds
genes
Genes
Small Untranslated RNA
gene expression
Gene Targeting
Gene Expression Profiling
assays

ASJC Scopus subject areas

  • Immunology

Cite this

Skalsky, R., Samols, M. A., Plaisance, K. B., Boss, I. W., Riva, A., Lopez, M. C., ... Renne, R. (2007). Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. Journal of Virology, 81(23), 12836-12845. https://doi.org/10.1128/JVI.01804-07

Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. / Skalsky, Rebecca; Samols, Mark A.; Plaisance, Karlie B.; Boss, Isaac W.; Riva, Alberto; Lopez, M. Cecilia; Baker, Henry V.; Renne, Rolf.

In: Journal of Virology, Vol. 81, No. 23, 12.2007, p. 12836-12845.

Research output: Contribution to journalArticle

Skalsky, R, Samols, MA, Plaisance, KB, Boss, IW, Riva, A, Lopez, MC, Baker, HV & Renne, R 2007, 'Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155', Journal of Virology, vol. 81, no. 23, pp. 12836-12845. https://doi.org/10.1128/JVI.01804-07
Skalsky R, Samols MA, Plaisance KB, Boss IW, Riva A, Lopez MC et al. Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. Journal of Virology. 2007 Dec;81(23):12836-12845. https://doi.org/10.1128/JVI.01804-07
Skalsky, Rebecca ; Samols, Mark A. ; Plaisance, Karlie B. ; Boss, Isaac W. ; Riva, Alberto ; Lopez, M. Cecilia ; Baker, Henry V. ; Renne, Rolf. / Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. In: Journal of Virology. 2007 ; Vol. 81, No. 23. pp. 12836-12845.
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abstract = "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 KSHV-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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AU - Samols, Mark A.

AU - Plaisance, Karlie B.

AU - Boss, Isaac W.

AU - Riva, Alberto

AU - Lopez, M. Cecilia

AU - Baker, Henry V.

AU - Renne, Rolf

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AB - 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 KSHV-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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