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)

被引:3
作者
Huang, Yujing [1 ,2 ,3 ]
Guo, Xin [4 ]
Zhang, Jing [1 ,2 ]
Li, Jianming [1 ,2 ,3 ]
Xu, Mingyi [1 ,2 ,3 ]
Wang, Qing [1 ]
Liu, Zhongyang [1 ,2 ,3 ]
Ma, Yanping [1 ,2 ,3 ]
Qi, Ying [1 ,2 ,3 ]
Ruan, Qiang [1 ,2 ,3 ]
机构
[1] China Med Univ, Virol Lab, Shengjing Hosp, Shenyang 110004, Peoples R China
[2] China Med Univ, Shengjing Hosp, Dept Pediat, Shenyang 110004, Peoples R China
[3] China Med Univ, Shengjing Hosp, Dept Obstet & Gynecol, Shenyang 110004, Peoples R China
[4] China Med Univ, Affiliated Hosp 4, Dept Pediat, Shenyang 110033, Peoples R China
基金
中国国家自然科学基金;
关键词
Human cytomegalovirus (HCMV); RNA2; 7; RNA polymerase II (Pol II); Cyclin-dependent kinase 9 (CDK9); Phosphorylation;
D O I
10.1016/j.virs.2022.02.011
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:358 / 369
页数:12
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