Activator-mediator binding stabilizes RNA polymerase II orientation within the human mediator-RNA polymerase II-TFIIF assembly.

Journal of Molecular Biology
Carrie Bernecky, Dylan J Taatjes

Abstract

The human Mediator complex controls RNA polymerase II (pol II) function in ways that remain incompletely understood. Activator-Mediator binding alters Mediator structure, and these activator-induced structural shifts appear to play key roles in regulating transcription. A recent cryo-electron microscopy (EM) analysis revealed that pol II adopted a stable orientation within a Mediator-pol II-TFIIF assembly in which Mediator was bound to the activation domain of viral protein 16 (VP16). Whereas TFIIF was shown to be important for orienting pol II within this assembly, the potential role of the activator was not assessed. To determine how activator binding might affect pol II orientation, we isolated human Mediator-pol II-TFIIF complexes in which Mediator was not bound to an activator. Cryo-EM analysis of this assembly, coupled with pol II crystal structure docking, revealed that pol II binds Mediator at the same general location; however, in contrast to VP16-bound Mediator, pol II does not appear to stably orient in the absence of an activator. Variability in pol II orientation might be important mechanistically, perhaps to enable sense and antisense transcription at human promoters. Because Mediator interacts extensively with po...Continue Reading

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Citations

Aug 22, 2013·Nucleic Acids Research·Thierry LacombeLaurent Kuras
Sep 6, 2013·Nucleic Acids Research·Sarah K LeeLaurie A Stargell
Jan 21, 2016·Nature·Carrie BerneckyPatrick Cramer
Sep 18, 2012·Biochimica Et Biophysica Acta·Ronald C Conaway, Joan Weliky Conaway
Oct 4, 2013·Critical Reviews in Biochemistry and Molecular Biology·Zachary C PossDylan J Taatjes
Feb 19, 2015·Nature Reviews. Molecular Cell Biology·Sarah SainsburyPatrick Cramer
Feb 19, 2015·Nature Reviews. Molecular Cell Biology·Benjamin L Allen, Dylan J Taatjes
Dec 7, 2016·Genes & Development·Sameer K SinghWei-Li Liu
Sep 16, 2017·The Journal of Biological Chemistry·Thomas M Harper, Dylan J Taatjes
Apr 3, 2020·Genes & Development·Allison C Schier, Dylan J Taatjes
Mar 7, 2014·The Journal of Biological Chemistry·Melissa A Mullen DavisDonal S Luse

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