title: A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
authors.forename: Paulina H
authors.initials: PH
authors.lastname: Wanrooij
authors.forename: Jay P
authors.initials: JP
authors.lastname: Uhler
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Fredrik
authors.initials: F
authors.lastname: Westerlund
authors.forename: Maria
authors.initials: M
authors.lastname: Falkenberg
authors.forename: Claes M
authors.initials: CM
authors.lastname: Gustafsson
mesh_terms: D002942:Circular Dichroism; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D012313:RNA / Q000737:chemistry*; D000077278:RNA, Mitochondrial; D061806:Transcription Termination, Genetic; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; C034477:RNA primers; D000077278:RNA, Mitochondrial; D012313:RNA