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| Status |
Public on Aug 19, 2015 |
| Title |
Herpesvirus saimiri microRNAs Preferentially Target Host Cell-Cycle Regulators |
| Organism |
Callithrix jacchus |
| Experiment type |
Other
Non-coding RNA profiling by high throughput sequencing
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| Summary |
In latently-infected marmoset T cells, Herpesvirus saimiri (HVS) expresses six microRNAs (known as miR-HSURs). The viral miR-HSURs are processed from chimeric primary transcripts, each containing a noncoding U-rich RNA (HSUR) and a pre-miRNA hairpin. To uncover functions of miR-HSURs, we identified mRNA targets in infected cells using High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation (HITS-CLIP). HITS-CLIP revealed hundreds of robust Argonaute (Ago) binding sites mediated by miR-HSURs in the host genome, but few in the HVS genome. Gene Ontology analysis showed that several pathways regulating the cell cycle are enriched among cellular targets of miR-HSURs. Interestingly, miR-HSUR4-3p represses expression of the p300 transcriptional co-activator by binding the open reading frame of its mRNA. miR-HSUR5-3p directly regulates BiP, an endoplasmic reticulum (ER) localized chaperone facilitating maturation of the Major Histocompatibility Complex I (MHC I) and the antiviral response. miR-HSUR5-3p also robustly downregulates WEE1, a key negative regulator of cell-cycle progression, leading to reduced phosphorylation of its substrate cyclin-dependent kinase (Cdk1). Consistently, inhibition of miR-HSUR5-3p in HVS-infected cells decreases their proliferation. Together, our results shed light on the roles of viral miRNAs in cellular transformation and viral latency.
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| Overall design |
Ago HITS-CLIP analysis and small RNA-Seq in HVS infected marmoset T cells
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| Contributor(s) |
Guo YE, Oei T, Steitz JA |
| Citation(s) |
26292323 |
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| Submission date |
Aug 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Yang Eric Guo |
| E-mail(s) |
eric.guo@wi.mit.edu
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| Organization name |
Whitehead Institute MIT
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| Lab |
Young
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| Street address |
455 Main St
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (2) |
| GPL17712 |
Illumina HiSeq 2000 (Callithrix jacchus) |
| GPL18304 |
Illumina Genome Analyzer II (Callithrix jacchus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA292108 |
| SRA |
SRP062128 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71806_CLIP_HVS.bedGraph.gz |
31.2 Kb |
(ftp)(http) |
BEDGRAPH |
| GSE71806_CLIP_cj3.bed.gz |
28.6 Mb |
(ftp)(http) |
BED |
| GSE71806_RAW.tar |
10.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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