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Investigation of functional roles of transcription termination factor-1 (TTF-I) in HIV-1 replication

  • Park, Seong-Hyun (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Yu, Kyung-Lee (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Jung, Yu-Mi (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Lee, Seong-Deok (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Kim, Min-Jeong (Avixgen Inc.) ;
  • You, Ji-Chang (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea)
  • Received : 2018.02.10
  • Accepted : 2018.03.17
  • Published : 2018.07.31

Abstract

Transcription termination factor-1 (TTF-I) is an RNA polymerase 1-mediated transcription terminator and consisting of a C-terminal DNA-binding domain, central domain, and N-terminal regulatory domain. This protein binds to a so-called 'Sal box' composed of an 11-base pair motif. The interaction of TTF-I with the 'Sal box' is important for many cellular events, including efficient termination of RNA polymerase-1 activity involved in pre-rRNA synthesis and formation of a chromatin loop. To further understand the role of TTF-I in human immunodeficiency virus (HIV)-I virus production, we generated various TTF-I mutant forms. Through a series of studies of the over-expression of TTF-I and its derivatives along with co-transfection with either proviral DNA or HIV-I long terminal repeat (LTR)-driven reporter vectors, we determined that wild-type TTF-I downregulates HIV-I LTR activity and virus production, while the TTF-I Myb-like domain alone upregulated virus production, suggesting that wild-type TTF-I inhibits virus production and trans-activation of the LTR sequence; the Myb-like domain of TTF-I increased virus production and trans-activated LTR activity.

Keywords

References

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