title: Transcription elongation regulator 1 (TCERG1) regulates competent RNA polymerase II-mediated elongation of HIV-1 transcription and facilitates efficient viral replication.
abstract: 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.
authors.forename: Mayte
authors.initials: M
authors.lastname: Coiras
authors.forename: Marta
authors.initials: M
authors.lastname: Montes
authors.forename: Immaculada
authors.initials: I
authors.lastname: Montanuy
authors.forename: María Rosa
authors.initials: MR
authors.lastname: López-Huertas
authors.forename: Elena
authors.initials: E
authors.lastname: Mateos
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Sommer
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández-Munain
authors.forename: José
authors.initials: J
authors.lastname: Alcamí
authors.affiliation: Department of Molecular Biology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Armilla, Granada 18016, Spain. csune@ipb.csic.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suñé
mesh_terms: D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C108440:TCERG1 protein, human; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II