A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop
Journal article, 2012

In human mitochondria the transcription machinery generates the RNA primers needed for initiation of DNA replication. A critical feature of the leading-strand origin of mitochondrial DNA replication is a CG-rich element denoted conserved sequence block II (CSB II). During transcription of CSB II, a G-quadruplex structure forms in the nascent RNA, which stimulates transcription termination and primer formation. Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. We here demonstrate that the unusual behavior of the RNA primer is explained by the formation of a stable G-quadruplex structure, involving the CSB II region in both the nascent RNA and the non-template DNA strand. Based on our data, we suggest that G-quadruplex formation between nascent RNA and the non-template DNA strand may be a regulated event, which decides the fate of RNA primers and ultimately the rate of initiation of DNA synthesis in human mitochondria.

primer

human pif1 helicase

formation

transcription termination

sequence

polymerase

strand origin

replication

binding protein

in-vitro

twinkle

Author

Paulina Wanrooij

University of Gothenburg

Jay Uhler

University of Gothenburg

Yonghong Shi

University of Gothenburg

Fredrik Westerlund

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Maria Falkenberg

University of Gothenburg

Claes M Gustafsson

University of Gothenburg

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 40 20 10334-10344

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Life Science Engineering (2010-2018)

Subject Categories

Biochemistry and Molecular Biology

DOI

10.1093/nar/gks802

More information

Created

10/8/2017