Dysregulation of the miR-30c/DLL4 axis by circHIPK3 is essential for KSHV lytic replication
Journal article
Harper, K.L., Mottram, T.J., Anene, C., Foster, B., Patterson, M.R., McDonnell, E., Macdonald, A., Westhead, D. and Whitehouse, A. (2022). Dysregulation of the miR-30c/DLL4 axis by circHIPK3 is essential for KSHV lytic replication. EMBO Reports. (e54117). https://doi.org/10.15252/embr.202154117
Authors | Harper, K.L., Mottram, T.J., Anene, C., Foster, B., Patterson, M.R., McDonnell, E., Macdonald, A., Westhead, D. and Whitehouse, A. |
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Abstract | 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 identify 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. |
Year | 2022 |
Journal | EMBO Reports |
Journal citation | (e54117) |
Publisher | EMBO Press |
Digital Object Identifier (DOI) | https://doi.org/10.15252/embr.202154117 |
Web address (URL) | https://www.embopress.org/doi/full/10.15252/embr.202154117 |
Publication dates | |
03 Mar 2022 | |
Publication process dates | |
Accepted | 18 Feb 2022 |
Deposited | 30 Mar 2022 |
Publisher's version | License File Access Level Open |
Accepted author manuscript |
https://openresearch.lsbu.ac.uk/item/8z995
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Publisher's version
EMBO Reports - 2022 - Harper - Dysregulation of the miR‐30c DLL4 axis by circHIPK3 is essential for KSHV lytic replication.pdf | ||
License: CC BY 4.0 | ||
File access level: Open |
Accepted author manuscript
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