Investigation of functional roles of transcription termination factor-1 (TTF-I) in HIV-1 replication
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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.
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.
참고문헌 (20)
- Grummt I, "A repeated 18 bp sequence motif in the mouse rDNA spacer mediates binding of a nuclear factor and transcription termination", Cell, 45, pp.837~846 (1986)[DOI]
- Putter V, "Transcription termination factor TTF-I exhibits contrahelicase activity during DNA replication", EMBO Rep, 3, pp.147~152 (2002)[DOI]
- Nemeth A, "The chromatin remodeling complex NoRC and TTF-I cooperate in the regulation of the mammalian rRNA genes in vivo", Nucleic Acids Res, 32, pp.4091~4099 (2004)[DOI]
- Clos J, "The core promoter of mouse rDNA consists of two functionally distinct domains", Nucleic Acids Res, 14, pp.7581~7595 (1986)[DOI]
- Strohner R, "NoRC--a novel member of mammalian ISWI-containing chromatin remodeling machines", EMBO J, 20, pp.4892~4900 (2001)[DOI]
- Diermeier SD, "Chromatin-specific regulation of mammalian rDNA transcription by clustered TTF-I binding sites", PLoS Genet, 9, pp.e1003786~ (2013)[DOI]
- Sander EE, "Oligomerization of the transcription termination factor TTF-I: implications for the structural organization of ribosomal transcription units", Nucleic Acids Res, 25, pp.1142~1147 (1997)[DOI]
- Nemeth A, "Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes", EMBO J, 27, pp.1255~1265 (2008)[DOI]
- Evers R, "Molecular coevolution of mammalian ribosomal gene terminator sequences and the transcription termination factor TTF-I", Proc Natl Acad Sci U S A, 92, pp.5827~5831 (1995)[DOI]
- Langst G, "RNA polymerase I transcription on nucleosomal templates: the transcription termination factor TTF-I induces chromatin remodeling and relieves transcriptional repression", EMBO J, 16, pp.760~768 (1997)[DOI]
- Langst G, "TTF-I determines the chromatin architecture of the active rDNA promoter", EMBO J, 17, pp.3135~3145 (1998)[DOI]
- Morrow BE, "A bipartite DNA-binding domain in yeast Reb1p", Mol Cell Biol, 13, pp.1173~1182 (1993)[DOI]
- Kanei-Ishii C, "The tryptophan cluster: a hypothetical structure of the DNA-binding domain of the myb protooncogene product", J Biol Chem, 265, pp.19990~19995 (1990)
- Sander EE, "The amino-terminal domain of the transcription termination factor TTF-I causes protein oligomerization and inhibition of DNA binding", Nucleic Acids Res, 24, pp.3677~3684 (1996)[DOI]
- Evers R, "Different domains of the murine RNA polymerase I-specific termination factor mTTF-I serve distinct functions in transcription termination", EMBO J, 14, pp.1248~1256 (1995)
- Smid A, "Limited proteolysis unmasks specific DNA-binding of the murine RNA polymerase I-specific transcription termination factor TTFI", J Mol Biol, 227, pp.635~647 (1992)[DOI]
- Dasgupta P, "Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription", Proc Natl Acad Sci U S A, 87, pp.8090~8094 (1990)[DOI]
- Churchill MJ, "c-Myb influences HIV type 1 gene expression and virus production", AIDS Res Hum Retroviruses, 17, pp.1481~1488 (2001)[DOI]
- Lessard F, "The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I", Mol Cell, 38, pp.539~550 (2010)[DOI]
- 김병수, "Identification of a novel type of small molecule inhibitor against HIV-1", BMB Reports, 48(2), pp.121~126 (2015), 생화학분자생물학회