Identification of viral ncRNA-mRNA interactions in Herpesvirus saimiri-infected marmoset T cells
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ABSTRACT: Viruses express several classes of non-coding (nc) RNAs1. For most of them, the functions and mechanisms by which they act are unknown. Herpesvirus saimiri (HVS), a g-herpesvirus that establishes latency in T cells of New World primates and has the ability to cause aggressive leukemias and lymphomas in non-natural hosts2, expresses seven small nuclear (sn), U-rich ncRNAs called HSURs in latently infected cells3-5. HSURs associate with Sm proteins and share biogenesis and structural features with cellular Sm-class snRNAs4,6. One of these viral snRNAs, HSUR 2, base-pairs with two host microRNAs (miRNAs), miR-142-3p and miR-167. However, HSUR 2 does not affect the abundance or activity of these two cellular miRNAs, suggesting alternative functions for these interactions. Here we show that HSUR 2 also base-pairs with messenger RNAs (mRNAs) in infected cells. We combined in vivo psoralen-mediated RNA-RNA crosslinking and high-throughput sequencing to identify mRNAs targeted by HSUR 2. HSUR 2 targets include mRNAs encoding Retinoblastoma (pRb) and factors involved in p53 signaling and apoptosis. We show that HSUR 2 represses expression of target mRNAs. Base-pairing between HSUR 2 and miR-142-3p and miR-16 is essential for HSUR 2-mediated mRNA repression, suggesting that HSUR 2 recruits these two cellular miRNAs to target mRNAs. Moreover, we show that HSUR 2 utilizes this mechanism to inhibit apoptosis. Our results uncover a role for a viral Sm-class RNA as a miRNA adaptor in post pre-mRNA-processing regulation of gene expression.
ORGANISM(S): Callithrix jacchus
PROVIDER: GSE79082 | GEO | 2017/10/01
SECONDARY ACCESSION(S): PRJNA314902
REPOSITORIES: GEO
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