PT  - JOURNAL ARTICLE
AU  - Katherine L. Harper
AU  - Timothy J. Mottram
AU  - Chinedu A. Anene
AU  - Becky Foster
AU  - Molly R. Patterson
AU  - Euan McDonnell
AU  - Andrew Macdonald
AU  - David Westhead
AU  - Adrian Whitehouse
TI  - CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication
AID  - 10.1101/2021.10.07.463491
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.07.463491
4099  - http://biorxiv.org/content/early/2021/10/08/2021.10.07.463491.short
4100  - http://biorxiv.org/content/early/2021/10/08/2021.10.07.463491.full
AB  - Non-coding RNA (ncRNA) regulatory networks are emerging as critical regulators of gene expression. These intricate networks of ncRNA:ncRNA interactions modulate multiple cellular pathways and impact the development and progression of multiple diseases. Herpesviruses, including Kaposi’s sarcoma-associated herpesvirus, are adept at utilising ncRNAs, encoding their own as well as dysregulating host ncRNAs to modulate virus gene expression and the host response to infection. Research has mainly focused on unidirectional ncRNA-mediated regulation of target protein-coding transcripts; however, we have identified a novel host ncRNA regulatory network essential for KSHV lytic replication in B cells. KSHV-mediated upregulation of the host cell circRNA, circHIPK3, is a key component of this network, functioning as a competing endogenous RNA of miR-30c, leading to increased levels of the miR-30c target, DLL4. Dysregulation of this network highlights a novel mechanism of cell cycle control during KSHV lytic replication in B cells. Importantly, disruption at any point within this novel ncRNA regulatory network has a detrimental effect on KSHV lytic replication, highlighting the essential nature of this network and potential for therapeutic intervention.Competing Interest StatementThe authors have declared no competing interest.