Abstract
Herpesviruses have evolved to encode multiple microRNAs [viral miRNAs (v-miRs)], a unique feature of this family of double stranded DNA (dsDNA) viruses. However, functional role of these v-miRs in host-pathogen interaction remains poorly studied. In this data, we examined the impact of oral disease associated v-miRs viz., miR-H1 [encoded by herpes simplex virus 1 (HSV1)] and miR-K12-3 [encoded by Kaposi sarcoma-associated herpesvirus (KSHV)] by identifying putative targets of viral miRNAs. We used our published microarray data (GSE107005) to identify the transcripts downregulated by the v-miRs. The 3′ untranslated region (UTR) of these genes were extracted using BioMart tool on Ensembl and subjected to RNA:RNA interaction employing RNA Hybrid. We obtained hundreds of potential and novel miR-H1 and miR-K12-3 binding sites on the 3′UTR of the genes downregulated by these v-miRs. The information can provide likely regulatory mechanisms of the candidate v-miRs through which they can exert biological impact during herpesvirus infection and pathogenesis.
Specifications Table
| Subject area | Biology |
| More specific subject area | Molecular Virology |
| Type of data | Text file |
| How data was acquired | Microarray and Bioinformatics |
| Data format | Filtered and analyzed |
| Experimental factors | Cells were transfected with v-miRs or control mimics |
| Experimental features | Genes downregulated by v-miRs were scanned for putative miRNA binding sites on the 3'UTR using RNA Hybrid tool. |
| Data source location | NA |
| Data accessibility | Data is presented as supporting file text with this manuscript. Microarray data of transcriptome wide changes in miR-H1 and miR-K12-3 overexpressing human oral keratinocytes compared to control mimics is deposited in the Gene Expression Omnibus public database under Accession Number GSE107005 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE107005). |
Value of the data
The data presented is valuable for the reasons listed below:
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The data provided here enlists human genes that were downregulated by herpesvirus derived miRNAs viz., miR-H1 (Herpes simplex virus 1) and miR-K12-3 (Kaposi sarcoma-associated herpesvirus) and harbor potential v-miR binding sites.
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These genes can provide new avenues to begin focused research on the role of viral miRNAs viz., miR-H1 and miR-K12-3 in the pathogenesis of oral mucosal diseases.
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Due to lack of online tools that can predict viral miRNA binding sites with high confidence, this methodology can provide a starting point to share large datasets examining global impact of v-miRs to identify more reliable candidate targets or facilitate development of algorithms to predict v-miR targets with a high degree of confidence.
1. Data
Human Herpesviruses (HHV) are dsDNA viruses that are highly prevalent worldwide [1]. A key feature of all herpesviruses is their capability to encode microRNAs [2]. These small non-coding RNAs are implicated in wide range of biological functions that govern host-pathogen interaction [2]. Recent evidences show a likely association of herpesvirus in oral diseases, however a role of viral components in the oral pathogenesis remains unknown [3], [4]. We recently identified four viral miRNAs that were upregulated in human subjects with inflamed pulps and diseased gingival biopsies compared with healthy tissues [5], [6]. Our recent transcriptome and miRnome analysis showed v-miRs can profoundly impact a specific set of genes in oral keratinocytes which are targeted by herpesviruses [6], [7]. However, the direct gene targets of these viral miRNAs will shed light on the possible pathways through which viral miRNAs can modulate host cell functions. The data presented here provides a list of potential miR-H1 and miR-K12-3 binding sites on the 3'UTR of host transcripts that were significantly downregulated by these v-miRs in our previously published microarray (GSE107005). Table 1, Table 2 provides list of some representative interaction for miR-H1 and miR-K12-3, respectively, identified in our screening. The remaining interactions are listed as supplementary information in the Supplementary text file 1 (for miR-H1) and Supplementary text file 2 (for miR-K12-3).
Table 1.
Predicted miR-H1-5p binding sites on the downregulated host genes. Sequence alignment of selected potential miR-H1-5p binding sites is shown. Only the binding sites with mfe<−20 kcal/mol are shown.
| v-miRNA | Target gene | vmiR and target gene sequence alignment |
|---|---|---|
| hsv1-miR-H1–5p | PREPL | Position 2928 |
| Target 5′ A UU G A 3′ | ||
| UCAUUUC GU UCUUCUAUU | ||
| GGUGAAG CA GGAAGGUAG | ||
| miRNA 3′ GG 5′ | ||
| hsv1-miR-H1–5p | TTC33 | Position 899 |
| Target 5′ U AA AA A 3′ | ||
| CCA UUUU CCUUUCGUC | ||
| GGU AGGG GGAAGGUAG | ||
| miRNA 3′ GA CA 5′ | ||
| hsv1-miR-H1–5p | ATG16L1 | Position 1965 |
| Target 5′ A AG U A A 3′ | ||
| CUACU C CUG CCUUCCAU | ||
| GGUGA G GGC GGAAGGUA | ||
| miRNA 3′ A A G 5' | ||
| hsv1-miR-H1–5p | NOTCH2NL | Position 2443 |
| Target 5′ G G G U G 3′ | ||
| CA U CCC UCCUUCCAUU | ||
| GU A GGG AGGAAGGUAG | ||
| miRNA 3′ G G A C 5′ | ||
| hsv1-miR-H1–5p | ZNF106 | Position 1227 |
| Target 5′ G A U 3′ | ||
| UCGCUUUCC G CCUUUUGUU | ||
| GGUGAAGGG C GGAAGGUAG | ||
| miRNA 3′ A 5′ | ||
| hsv1-miR-H1–5p | CHML | Position 212 |
| Target 5′ A AC AU A 3′ | ||
| UCAC CUC UUCUUUCAUC | ||
| GGUG GGG AGGAAGGUAG | ||
| miRNA 3′ AA C 5′ | ||
| hsv1-miR-H1–5p | CCDC91 | Position 464 |
| Target 5′ A CC AC G 3′ | ||
| CAUU CCC UCUUUCCAU | ||
| GUGA GGG AGGAAGGUA | ||
| miRNA 3′ G A C G 5′ | ||
| hsv1-miR-H1–5p | RABEP1 | Position 88 |
| Target 5′ C A 3′ | ||
| CCAUUUUUC UUUUUCUGU | ||
| GGUGAAGGG AGGAAGGUA | ||
| miRNA 3′ C G 5′ | ||
| hsv1-miR-H1–5p | TGFBR1 | Position 4034 |
| Target 5′ G A 3′ | ||
| UACUUUCUG UUUUCUGU | ||
| GUGAAGGGC GGAAGGUA | ||
| miRNA 3′ G A G 5′ | ||
| hsv1-miR-H1–5p | TRIM52 | Position 453 |
| Target 5′ G C UU A 3′ | ||
| UACU C GUUUUUCUGUU | ||
| GUGA G CAGGAAGGUAG | ||
| miRNA 3′ G A GG 5′ | ||
| hsv1-miR-H1–5p | DYM | Position 8446 |
| Target 5′A A A G 3′ | ||
| UACUU UG UCUUUCCAUU | ||
| GUGAA GC AGGAAGGUAG | ||
| miRNA 3′ G G 5′ | ||
| hsv1-miR-H1–5p | NDUFS1 | Position 1742 |
| Target 5′ A A CA C 3′ | ||
| GCUGU UGUUU CAGAGUGUG | ||
| CGACG GCAGG GUCUUACAC | ||
| miRNA 3′ AG A U 5′ | ||
| hsv1-miR-H1–5p | SLC4A7 | Position 1345 |
| Target 5′ U UG G G 3′ | ||
| UACU UUU GUCCUUUUAU | ||
| GUGA AGG CAGGAAGGUA | ||
| miRNA 3′ G G G 5′ | ||
| hsv1-miR-H1–5p | PRRC1 | Position 47 |
| Target 5′ G C U 3′ | ||
| UAC UUCC UCCUUUUGUU | ||
| GUG AGGG AGGAAGGUAG | ||
| miRNA 3′ G A C 5′ | ||
| hsv1-miR-H1–5p | IL1RAP | Position 2670 |
| Target 5′ U A U A 3′ | ||
| UACUU UU UCUUUCCAU | ||
| GUGAA GG AGGAAGGUA | ||
| miRNA 3′ G G C G 5′ |
Table 2.
Predicted miR-K12-3 binding sites on the downregulated host genes. Sequence alignment of selected potential miR-K12-3 binding sites on the predicted targets is shown. Only the binding sites with mfe<−20 kcal/mol are listed.
| v-miRNA | Target gene | vmiR and target gene sequence alignment |
|---|---|---|
| kshv-miR-K12-3 | CBX5 | Position 8806 |
| Target 5′ U AUC G U 3′ | ||
| UC UUGUU U UUGGAAUGUGA | ||
| AG GACGG G AGUCUUACACU | ||
| miRNA 3′ CCA G 5′ | ||
| kshv-miR-K12-3 | GOLGA3 | Position 3592 |
| Target 5′ G AGU GA A 3′ | ||
| GC GU UUCU UAGGAUGUGA | ||
| CG CG AGGA GUCUUACACU | ||
| miRNA 3′ AG AGC 5′ | ||
| kshv-miR-K12-3 | UIMM21 | Position 55 |
| Target 5′ AU 3′ | ||
| GCUGCC UUC CAGAAUGUG | ||
| CGACGG AGG GUCUUACAC | ||
| miRNA 3′ AG C AU 5′ | ||
| kshv-miR-K12-3 | UBL1X | Position 2516 |
| Target 5′ GU A G U A 3′ | ||
| GCU U GUCUU A GAAUGUGA | ||
| CGA G CAGGA U CUUACACU | ||
| miRNA 3′ AG C G G5′ | ||
| kshv-miR-K12-3 | FKBP14 | Position 1178 |
| Target 5′ AAA AG U U 3′ | ||
| CUG GUU C GGGUGUGG | ||
| GAC CAG G CUUACACU | ||
| miRNA 3′ AGC GG GA U 5′ | ||
| kshv-miR-K12-3 | DSUN | Position 659 |
| Target 5′ A A GAG A C 3′ | ||
| UC UUGU UGUCUUC G GAAUGUG | ||
| AG GACG GCAGGAG U CUUACAC | ||
| miRNA 3′ CU 5′ | ||
| kshv-miR-K12-3 | ORC2 | Position 372 |
| Target 5′ G GU A 3′ | ||
| UGU UUGUUC CAGAGUGUGG | ||
| GCG GGCAGG GUCUUACACU | ||
| miRNA 3′ A AC A5′ | ||
| kshv-miR-K12-3 | COPA | Position 33 |
| Target 5′ A CC AG U 3′ | ||
| UGUU CC CC AGAAUGUG | ||
| GCGA GG GG UCUUACAC | ||
| miRNA 3′ A CCA AG U 5′ | ||
| kshv-miR-K12-3 | POLR3B | Position 228 |
| Target 5′ G UAU A AG U C 3′ | ||
| GCUGC UG UC C A GGAUGUGA | ||
| CGACG GC AG G U CUUACACU | ||
| miRNA 3′ AG AG 5′ | ||
| kshv-miR-K12-3 | RAB3D | Position 260 |
| Target 5′ C UU 3′ | ||
| UUGCUGCU UCC AGGGUGUG | ||
| AGCGACGG AGG UCUUACAC | ||
| miRNA 3′ CAG U 5′ | ||
| kshv-miR-K12-3 | SLC1A4 | Position 2435 |
| Target 5′ G G GC 3′ | ||
| G UGCU UCC AGAGUGUG | ||
| C ACGG AGG UCUUACAC | ||
| miRNA 3′ AG G CAG U 5′ | ||
| kshv-miR-K12-3 | CCND2 | Position 1742 |
| Target 5′ AAA CA C 3′ | ||
| GCUGU UGUUU CAGAGUGUG | ||
| CGACG GCAGG GUCUUACAC | ||
| miRNA 3′ AG AU 5′ | ||
| kshv-miR-K12-3 | CD101 | Position 48 |
| Target 5′ A GAA A 3′ | ||
| UUG GCU CC AGGGUGUGA | ||
| AGC CGG GG UCUUACACU | ||
| miRNA 3′ GA CA AG 5′ | ||
| kshv-miR-K12-3 | RAB40B | Position 98 |
| Target 5′ G AA GC U 3′ | ||
| CG UGCUG CUU GAAUGUG | ||
| GC ACGGC GGA CUUACAC | ||
| miRNA 3′ A G AGU U 5′ | ||
| kshv-miR-K12-3 | PIUPNM3 | Position 2628 |
| Target 5′ A GG GU U 3′ | ||
| GUUG CG U U GAGUGUG | ||
| CGAC GC G A CUUACAC | ||
| miRNA 3′ AG GA G GU U 5′ |
2. Experimental design, materials and methods
2.1. Primary gingival human oral keratinocyte (HOK) culture
Primary HOK (human gingival epithelial cells) were purchased from ScienCell Research Laboratories (Carlsbad, CA). Cultures were tested for HOK markers by immunofluorescent methods using antibodies to cytokeratine-8, -18 and -19 and were negative for Human Immunodeficiency Virus 1 (HIV-1), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), mycoplasma, bacteria, yeast and fungi. Cells were cultured using DermaLife K Keratinocyte Medium Complete Kit (Lifeline Cell Technology, Frederick, MD).
2.2. Transient miRNA transfections and total RNA isolation
Transient viral miRNA (miR-H1 or miR-K12-3) or control mimic transfections in HOK were performed using Lipofectamine 2000 reagent (Life Technologies, San Diego, CA) as described previously [8], [9]. Cells were transfected with viral miRNA mimics (Qiagen, Gaithsburg, MD, USA) at a final concentration of 15 nM for 36 h. Total RNA was isolated using the miRNeasy kit (Qiagen).
2.3. Microarray analysis
We used our published microarray data deposited in the Gene Expression Omnibus public database under Accession Number GSE107005 for the identification of putative viral miRNA target transcripts [6]. Array data were in compliance with Minimum Information About a Microarray Experiment (MIAME) guidelines.
2.4. V-miR target prediction of differentially downregulated genes
To identify miR-H1 and miR-K12-3 gene targets with high confidence, we first selected downregulated genes. The 3′UTR of these genes were extracted using BioMart tool on Ensembl (http://www.ensembl.org/biomart/martview/aa867419c3c6fd64f94af6d4a6549d3c). Briefly, we selected Ensembl Genes 87 database and Human Genes dataset (GRCh38.p7). Next, the "Filters" were selected to match the input genes list. In the "Gene" tab set the "ID list limit" filter to "HGNC symbol(s)". Finally, to procure the 3'UTR sequences “Attributes” were set. In the "Attributes", select "Sequences" and then select 3′UTR start and 3'UTR end, click "Ensembl Gene ID" and "Associated Gene Name". The results were exported to by selecting "File", "FASTA" and "Unique results only”. This was done separately for miR-H1 and miR-K12-3 datasets.
v-miR-target 3’UTR interaction was assessed by target prediction tool RNAHyrbid software (https://bibiserv2.cebitec.uni-bielefeld.de/rnahybrid?id=rnahybrid_view_submission). The procured 3′UTR sequences and miR-H1 and miR-K12-3 sequences (extracted from miRbase v.21) were provided as input for RNA Hybrid analysis. The stringency parameters were set-up for individual sequences and we opted for three hits per target to highlight any probable v-miR binding sequence present on the target.
We considered the following parameters to select putative v-miR regulated genes. (i) There should be high sequence complementarity in the seed region (positions 2–8 nt from 5′ of miRNA), with only 1 mismatch allowed. (ii) For stringency, we picked v-miR-target interactions where more than 11 nts of the v-miR sequence are involved in the interaction. (iii) If there is any mismatch in the seed regions, this should be compensated by strong binding beyond the seed region. (iv) The bulge in the interaction region should not involve more than 3 nucleotides. (v) Entropy of the v-miR-target interaction was set at stringent level with cut-off <22 kcal/mol.
Acknowledgements
Part of this work was funded by the NIH/NIDCR R21 DE026259-01A1 to ARN and NIH/NIDCR R01 DE02105201A1 to SN.
Footnotes
Transparency data associated with this article can be found in the online version at https://doi.org/10.1016/j.dib.2018.05.020.
Supplementary data associated with this article can be found in the online version at https://doi.org/10.1016/j.dib.2018.05.020.
Contributor Information
Afsar R. Naqvi, Email: afsarraz@uic.edu.
Salvador Nares, Email: snares@uic.edu.
Transparency document. Supplementary material
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Appendix A. Supplementary material
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