Host mRNA Export Block

Molecular Mechanism of KSHV ORF10 in Host mRNA Export Block

Our lab’s work in ORF10 was spearheaded by Dr. Danyang Gong and was published in Cell Host & Microbe. Previously, we showed that the viral protein, KSHV ORF10, restricts host mRNA export selectively through its interaction with a cellular RNA export factor, Rae1. The current working hypothesis is that the ORF10-Rae1 complex is directed to a target transcript through its interaction with an RNA-binding (RBP). In this study, we aim to identify the RBP that mediates RNA binding, as well as elucidate the 3’UTR mRNA motifs that convey selectivity. We also aim to validate host mRNAs potentially targeted by ORF10 for mRNA export inhibition in order to investigate the pathogenic role of ORF10. A long-term impact of the study is the elucidation of key players in selective mRNA export and its role in gene expression regulation. The dysregulation of host mRNA export could have significant contribution towards KSHV-related pathogenesis. Furthermore, the study also contributes further knowledge on how viruses are able to manipulate specific host functions to its own advantage.