Human cytomegalovirus RNA2.7 inhibits RNA polymerase II (Pol II) Serine-2 phosphorylation by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9).

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous pathogen belongs to betaherpesvirus subfamily. RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20% of total viral transcripts. In our study, functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant. It was demonstrated that RNA polymerase II (Pol II)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection. A 145 ​nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of Pol II Serine-2 (Pol II S2) by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9). Due to the loss of Pol II S2 phosphorylation, cellular DNA pre-replication complex (pre-RC) factors, including Cdt1 and Cdc6, were significantly decreased, which prevented more cells from entering into S phase and facilitated viral DNA replication. Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.

• Authors: Yujing Huang, Xin Guo, Jing Zhang, Jianming Li, Mingyi Xu, Qing Wang, Zhongyang Liu, Yanping Ma, Ying Qi, Qiang Ruan
• Journal: Virologica Sinica (Virol Sin) Vol. 37 Issue 3 Pg. 358-369 (Jun 2022) ISSN: 1995-820X [Electronic] Netherlands
• PMID: 35537980 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.

Chemical References

• DNA, Viral
• Serine
• Cyclin-Dependent Kinase 9
• RNA Polymerase II

Topics

• Cyclin-Dependent Kinase 9 (genetics, metabolism)
• Cytomegalovirus (genetics)
• DNA Replication
• DNA, Viral
• Phosphorylation
• RNA Polymerase II (genetics, metabolism)
• Serine (genetics)
• Virus Replication (genetics)