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    Open to better transcribe: hijacking of a molecular key involved in chromatin opening by the HTLV-1 transcriptional activator

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    Team Florence Margottin-Goguet & Claudine Pique

    Open to better transcribe

    The team of Claudine Pique demonstrates that the HTLV-1 Tax protein exploits the XPB subunit of the TFIIH complex during viral transcription. This study has been recently published in Journal of Virology.

    Human T-cell lymphotropic virus type 1 (HTLV-1) is responsible for a T-cell leukemia and diverse inflammatory disorders. Viral transcription is under the control of the viral regulatory Tax protein that functions by recruiting transcription factors to the promoter. Thus, Tax first recruits CREB and its co-factors to transactivate the viral promoter. Tax also controls subsequent steps of the transcription process by recruiting general transcription factors such as TFIIA and TFIID (preinitiation) as well as pTEFB (elongation). 

     

    The team of Florence Margottin-Goguet and Claudine Pique has found that Tax also controls the transition between preinitiation and elongation by targeting the TFIIH complex. Indeed, there data show that Tax directly interacts with, and recruits to the promoter, the XPB subunit of TFIIH. XPB catalyses the promoter opening step, a mechanism critical in the case of inducible transcription. In absence of XPB, Tax cannot transactivate the viral promoter anymore and the production of viral mRNA is shutdown. 

    This work reveals that via the recruitment of XPB, Tax targets the promoter opening step of the transcription process and therefore that this step is critical for optimal production of the viral mRNAs. Furthermore, this study provides the demonstration that Tax exerts a control on all the transcription steps, highlighting the amazing capacity of this viral protein to manipulate cellular machineries. 

    This study was funded by grants from the Ligue contre le Cancer, Fondation ARC, Fondation Recherche Médicale and Université Paris Descartes.

     

    Reference

    HTLV-1 transactivator Tax exploits the XPB subunit of TFIIH during viral transcription. Martella C, Tollenaere AI, Waast L, Lacombe B, Groussaud D, Margottin-Goguet F, Ramirez BC, Pique C. .J Virol. 2020 Feb 5. pii: JVI.02171-19. doi: 10.1128/JVI.02171-19. [Epub ahead of print]

     

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