@article{9b185b196a0946948b4e665a52db432a,
title = "Mechanism of Transcription Anti-termination in Human Mitochondria",
abstract = "In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA—the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream “sliding clamp,” providing high processivity to the EC. TEFM also binds near the RNA exit channel to prevent formation of the RNA G-quadruplex structure required for termination and thus synthesis of the replication primer. Our data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mtDNA. Crystal structures of the human mitochondrial transcription factor TEFM with its C-terminal domain bound to a transcription elongation complex provide insights into the molecular basis of its roles in promoting elongation and preventing termination.",
author = "Hillen, {Hauke S.} and Parshin, {Andrey V.} and Karen Agaronyan and Morozov, {Yaroslav I.} and Graber, {James J.} and Aleksandar Chernev and Kathrin Schwinghammer and Henning Urlaub and Michael Anikin and Patrick Cramer and Dmitry Temiakov",
note = "Funding Information: We thank past and present members of the Cramer laboratory, in particular, Gaurika Garg and J{\"u}rgen Wrawzinek. We thank the staff at the Swiss Light Source beamline X06SA and at the PETRA III storage ring at DESY Hamburg, in particular, Micele Cianci for assistance during diffraction data collection. We thank W.T. McAllister and M. Gottesman for critical reading of the manuscript and helpful discussion. Part of this work was performed at Beamlines X06SA and X10SA at the Swiss Light Source at the Paul-Scherrer-Institut, Villigen, Switzerland, and at PETRA-III, DESY Hamburg, Germany. This work was funded by NIH RO1 GM104231 and R01 GM118941 (D.T.), Deutsche Forschungsgemeinschaft ( SFB860 ) (P.C.), European Research Council ( Advanced Grant TRANSREGULON ) (P.C.), the Volkswagen Foundation (P.C.), and Deutsche Forschungsgemeinschaft SFB860 (H.U.). H.S.H. was supported by a Boehringer Ingelheim Fonds PhD student fellowship. Funding Information: We thank past and present members of the Cramer laboratory, in particular, Gaurika Garg and J?rgen Wawrzinek. We thank the staff at the Swiss Light Source beamline X06SA and at the PETRA III storage ring at DESY Hamburg, in particular, Micele Cianci for assistance during diffraction data collection. We thank W.T. McAllister and M. Gottesman for critical reading of the manuscript and helpful discussion. Part of this work was performed at Beamlines X06SA and X10SA at the Swiss Light Source at the Paul-Scherrer-Institut, Villigen, Switzerland, and at PETRA-III, DESY Hamburg, Germany. This work was funded by NIH RO1 GM104231 and R01 GM118941 (D.T.), Deutsche Forschungsgemeinschaft (SFB860) (P.C.), European Research Council (Advanced Grant TRANSREGULON) (P.C.), the Volkswagen Foundation (P.C.), and Deutsche Forschungsgemeinschaft SFB860 (H.U.). H.S.H. was supported by a Boehringer Ingelheim Fonds PhD student fellowship. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
day = "16",
doi = "10.1016/j.cell.2017.09.035",
language = "English (US)",
volume = "171",
pages = "1082--1093.e13",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}