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Herpesvirus saimiri microRNAs Preferentially Target Host Cell-Cycle Regulators

ABSTRACT: 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.

ORGANISM(S): Callithrix jacchus

PROVIDER: GSE71806 | GEO | 2015/08/19

SECONDARY ACCESSION(S): PRJNA292108

REPOSITORIES: GEO

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