TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA
Abstract Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (OH). A 7S DNA strand,...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07645-4 |
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| author | Shigeru Matsuda Masunari Nakayama Yura Do Takashi Ishiuchi Mikako Yagi Sjoerd Wanrooij Kazuto Nakada Fan-Yan Wei Kenji Ichiyanagi Hiroyuki Sasaki Dongchon Kang Takehiro Yasukawa |
| author_facet | Shigeru Matsuda Masunari Nakayama Yura Do Takashi Ishiuchi Mikako Yagi Sjoerd Wanrooij Kazuto Nakada Fan-Yan Wei Kenji Ichiyanagi Hiroyuki Sasaki Dongchon Kang Takehiro Yasukawa |
| author_sort | Shigeru Matsuda |
| collection | DOAJ |
| description | Abstract Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (OH). A 7S DNA strand, a presumed aborted replication product, is also synthesized from OH. Transition from RNA synthesis to DNA synthesis at OH is crucial for balancing replication with transcription, yet the mechanism remains unclear. Herein, we examine the role of mitochondrial transcription elongation factor (TEFM) in this process. TEFM knockout results in decreased 7S DNA, strand-asynchronous replication intermediates, and mtDNA copy number, all of which are concordant with downregulation of RNA-to-DNA transition at OH. Conversely, levels of tRNAs encoded near transcription promoters increase, indicating enhanced transcription initiation frequency. Taken together, we propose that, in addition to conferring processivity to the mitochondrial RNA polymerase, TEFM plays a crucial role in maintaining the balance between mitochondrial transcription and replication. |
| format | Article |
| id | doaj-art-bb808e1fd6dd4b0eac8afcf50ae4d47c |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-bb808e1fd6dd4b0eac8afcf50ae4d47c2025-02-09T12:50:48ZengNature PortfolioCommunications Biology2399-36422025-02-018111310.1038/s42003-025-07645-4TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNAShigeru Matsuda0Masunari Nakayama1Yura Do2Takashi Ishiuchi3Mikako Yagi4Sjoerd Wanrooij5Kazuto Nakada6Fan-Yan Wei7Kenji Ichiyanagi8Hiroyuki Sasaki9Dongchon Kang10Takehiro Yasukawa11Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDivision of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medical Biochemistry and Biophysics, Umeå UniversityInstitute of Life and Environmental Sciences, University of TsukubaDepartment of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya UniversityDivision of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu UniversityAbstract Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (OH). A 7S DNA strand, a presumed aborted replication product, is also synthesized from OH. Transition from RNA synthesis to DNA synthesis at OH is crucial for balancing replication with transcription, yet the mechanism remains unclear. Herein, we examine the role of mitochondrial transcription elongation factor (TEFM) in this process. TEFM knockout results in decreased 7S DNA, strand-asynchronous replication intermediates, and mtDNA copy number, all of which are concordant with downregulation of RNA-to-DNA transition at OH. Conversely, levels of tRNAs encoded near transcription promoters increase, indicating enhanced transcription initiation frequency. Taken together, we propose that, in addition to conferring processivity to the mitochondrial RNA polymerase, TEFM plays a crucial role in maintaining the balance between mitochondrial transcription and replication.https://doi.org/10.1038/s42003-025-07645-4 |
| spellingShingle | Shigeru Matsuda Masunari Nakayama Yura Do Takashi Ishiuchi Mikako Yagi Sjoerd Wanrooij Kazuto Nakada Fan-Yan Wei Kenji Ichiyanagi Hiroyuki Sasaki Dongchon Kang Takehiro Yasukawa TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA Communications Biology |
| title | TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA |
| title_full | TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA |
| title_fullStr | TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA |
| title_full_unstemmed | TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA |
| title_short | TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA |
| title_sort | tefm facilitates transition from rna synthesis to dna synthesis at h strand replication origin of mtdna |
| url | https://doi.org/10.1038/s42003-025-07645-4 |
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