Transcription elongation regulator 1 (TCERG1) regulates competent RNA polymerase II-mediated elongation of HIV-1 transcription and facilitates efficient viral replication

Retrovirology

Carlos Suñé¹  José Alcamí⁷  Cristina Hernández-Munain⁵  Mariano A Garcia-Blanco³  Caroline Le Sommer²  Elena Mateos⁷  María Rosa López-Huertas⁷  Immaculada Montanuy⁴  Marta Montes⁶  Mayte Coiras⁷ 

[1] Department of Molecular Biology, Instituto de Parasitología y Biomedicina “López Neyra” (IPBLN-CSIC), Armilla, Granada 18016, Spain;The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, Durham, NC 27709, USA;Department of Molecular Genetics and Microbiology, and Center for RNA Biology, Duke University Medical Center, 213 Research Drive, Durham, NC 27710, USA;Department of Medicine, University of Cambridge, Hills Road, Cambridge CB2 2QQ, United Kingdom;Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina “López Neyra” (IPBLN-CSIC), Armilla Granada 18016, Spain;Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen DK-2200, Denmark;AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

关键词: Pausing;    RNA polymerase II;    Transcription elongation;    TCERG1;   

Others  :  806749
DOI  :  10.1186/1742-4690-10-124

 received in 2013-04-08, accepted in 2013-10-18,  发布年份 2013

【 摘 要 】

Background

Control of RNA polymerase II (RNAPII) release from pausing has been proposed as a checkpoint mechanism to ensure optimal RNAPII activity, especially in large, highly regulated genes. HIV-1 gene expression is highly regulated at the level of elongation, which includes transcriptional pausing that is mediated by both viral and cellular factors. Here, we present evidence for a specific role of the elongation-related factor TCERG1 in regulating the extent of HIV-1 elongation and viral replication in vivo.

Results

We show that TCERG1 depletion diminishes the basal and viral Tat-activated transcription from the HIV-1 LTR. In support of a role for an elongation mechanism in the transcriptional control of HIV-1, we found that TCERG1 modifies the levels of pre-mRNAs generated at distal regions of HIV-1. Most importantly, TCERG1 directly affects the elongation rate of RNAPII transcription in vivo. Furthermore, our data demonstrate that TCERG1 regulates HIV-1 transcription by increasing the rate of RNAPII elongation through the phosphorylation of serine 2 within the carboxyl-terminal domain (CTD) of RNAPII and suggest a mechanism for the involvement of TCERG1 in relieving pausing. Finally, we show that TCERG1 is required for HIV-1 replication.

Conclusions

Our study reveals that TCERG1 regulates HIV-1 transcriptional elongation by increasing the elongation rate of RNAPII and phosphorylation of Ser 2 within the CTD. Based on our data, we propose a general mechanism for TCERG1 acting on genes that are regulated at the level of elongation by increasing the rate of RNAPII transcription through the phosphorylation of Ser2. In the case of HIV-1, our evidence provides the basis for further investigation of TCERG1 as a potential therapeutic target for the inhibition of HIV-1 replication

【 授权许可】

   
2013 Coiras et al.; licensee BioMed Central Ltd.

【 图 表 】

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