title: Termination factor-mediated DNA loop between termination and initiation sites drives mitochondrial rRNA synthesis.
abstract: The human mitochondrial transcription termination factor mTERF plays a central role in the control of heavy-strand rDNA transcription by promoting initiation, besides termination, of this transcription. However, until now, the mechanism underlying this stimulation of transcription by mTERF was not understood. In the present work, addition of mTERF to a HeLa cell mitochondrial lysate-based reaction mixture containing an artificial rDNA template did indeed specifically stimulate rDNA transcription. This stimulation required that mTERF be simultaneously bound to the rDNA transcription termination and initiation sites in the same molecule, thus forming a loop. Most significantly, a double binding of mTERF to the rDNA molecule, with resulting loop formation, was also shown in vivo. These results strongly suggest that, to satisfy the need for high rate of rDNA transcription, human mitochondrial rRNA synthesis involves mTERF-mediated rDNA looping that promotes recycling of the transcription machinery.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: Jaehyoung
authors.initials: J
authors.lastname: Cho
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cesare
authors.forename: Jack D
authors.initials: JD
authors.lastname: Griffith
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Attardi
mesh_terms: D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000737:chemistry; D012313:RNA / Q000096:biosynthesis / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013728:Terminator Regions, Genetic / Q000502:physiology*; D024363:Transcription Initiation Site / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; D035321:Telomeric Repeat Binding Protein 1; D012313:RNA; D004247:DNA