CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication
CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication
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 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.
McDonnell Euan、Harper Katherine L.、Mottram Timothy J.、Anene Chinedu A.、Foster Becky、Westhead David、Macdonald Andrew、Whitehouse Adrian、Patterson Molly R.
School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsCentre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of LondonSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds||Department of Biochemistry and Microbiology, Rhodes UniversitySchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds
基础医学分子生物学生物科学研究方法、生物科学研究技术
Kaposi’s sarcoma (KS)-associated herpesvirusncRNAsregulatory networkcircRNAs
McDonnell Euan,Harper Katherine L.,Mottram Timothy J.,Anene Chinedu A.,Foster Becky,Westhead David,Macdonald Andrew,Whitehouse Adrian,Patterson Molly R..CircHIPK3 dysregulation of the miR-30c/DLL4 axis is essential for KSHV lytic replication[EB/OL].(2025-03-28)[2025-06-06].https://www.biorxiv.org/content/10.1101/2021.10.07.463491.点此复制
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