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 Phil Shin, Wonkyun Ronny Im, Hwi Ho Lee, Jiyoung Joan 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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo 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.

Original languageEnglish
Pages (from-to)683-694
Number of pages12
JournalMolecular Therapy - Oncolytics
Volume24
DOIs
StatePublished - 17 Mar 2022

Keywords

  • Protein Kinase R
  • adenovirus
  • host tropism
  • kinesin
  • nc886
  • non-coding RNA
  • oncolytic virotherapy

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