title: A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site.
abstract: Human mitochondrial DNA contains a distinctive guanine-rich motif denoted conserved sequence block II (CSB II) that stops RNA transcription, producing prematurely terminated transcripts to prime mitochondrial DNA replication. Recently, we reported a general phenomenon that DNA:RNA hybrid G-quadruplexes (HQs) readily form during transcription when the non-template DNA strand is guanine-rich and such HQs in turn regulate transcription. In this work, we show that transcription of mitochondrial DNA leads to the formation of a stable HQ or alternatively an unstable intramolecular DNA G-quadruplex (DQ) at the CSB II. The HQ is the dominant species and contributes to the majority of the premature transcription termination. Manipulating the stability of the DQ has little effect on the termination even in the absence of HQ; however, abolishing the formation of HQs by preventing the participation of either DNA or RNA abolishes the vast majority of the termination. These results demonstrate that the type of G-quadruplexes (HQ or DQ) is a crucial determinant in directing the transcription termination at the CSB II and suggest a potential functionality of the co-transcriptionally formed HQ in DNA replication initiation. They also suggest that the competition/conversion between an HQ and a DQ may regulate the function of a G-quadruplex-forming sequence.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Ke-wei
authors.initials: KW
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Ren-yi
authors.initials: RY
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Yi-de
authors.initials: YD
authors.lastname: He
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Jia-yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Jia-quan
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China z.tan@ioz.ac.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
mesh_terms: D001483:Base Sequence; D017124:Conserved Sequence; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D009154:Mutation; D009841:Oligonucleotides / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000737:chemistry; D000077278:RNA, Mitochondrial; D013728:Terminator Regions, Genetic; D061806:Transcription Termination, Genetic
chemical_list: D004272:DNA, Mitochondrial; D009841:Oligonucleotides; D000077278:RNA, Mitochondrial; D012313:RNA