HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism

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During viral replication, the oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) modulates both host and viral gene expression. KSHV ORF57 is a multifunctional posttranscriptional regulator that is essential for viral replication and stabilizes viral RNAs. Previous studies demonstrated that ORF57 RNA-binding is essential for its activity, but the full spectrum of ORF57 targets are unknown. Here we employed a high-throughput analysis to identify RNA fragments bound by ORF57 during lytic reactivation. As expected, we found targets that mapped to the viral genome, and we further uncovered novel host targets, a subset of which had ORF57 bound near their 5´ ends. Further examination of this subset demonstrated that ORF57 bound preferentially at the 5´-most exon-intron boundary. ORF57 affected the pre-mRNA abundance from these genes, most likely by stabilizing otherwise unstable inefficiently spliced pre-mRNAs. In at least one case, this stabilization led to increases in mRNA expression of the host gene. We suggest that KSHV employs the same mechanism to stabilize intronless viral RNAs and cellular unspliced pre-mRNAs to modulate viral and host gene expression during lytic reactivation.

Vyšlo v časopise: HITS-CLIP Analysis Uncovers a Link between the Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein and Host Pre-mRNA Metabolism. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004652
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004652

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