A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus
Enkhjin Saruuldalai, Jiyoung Park, Dongmin Kang, Seung-Pil Shin, Wonkyun Ronny Im, Hwi‐Ho Lee, Ji-Young Jang, Jong‐Lyul Park, Seon‐Young Kim, Jung-Ah Hwang, Young‐Dong Kim, Jung‐Hoon Lee, Eun Jung Park, Yeon-Su Lee, In-Hoo Kim, Sang-Jin Lee, Yong Sun Lee
Abstract
model for preclinical evaluation of therapeutically engineered adenovirus. nc886 is a human non-coding RNA that suppresses Protein Kinase R (PKR), an antiviral protein. In this study, we have found that nc886 greatly promotes adenoviral gene expression and replication. Remarkably, the stimulatory effect of nc886 is not dependent on its function to inhibit PKR. Rather, nc886 facilitates the nuclear entry of adenovirus via modulating the kinesin pathway. nc886 is not conserved in mouse and, when xenogeneically expressed in mouse cells, promotes adenovirus replication. Our investigation has discovered a novel mechanism of how a host ncRNA plays a pro-adenoviral role. Given that nc886 expression is silenced in a subset of cancer cells, our study highlights that oncolytic virotherapy might be inefficient in those cells. Furthermore, our findings open future possibilities of harnessing nc886 to improve the efficacy of oncolytic adenovirus and to construct nc886-expressing transgenic mice as an animal model.