Document Type
Article
Publication Date
3-21-2022
Abstract
Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of the DNA in the initiation complex and permitted investigation of the sequence-specific protein-DNA interactions. We determined the molecular basis of promoter recognition by mtRNAP and TFB2M, which cooperatively recognize bases near TSS in a species-specific manner. Our findings reveal a role of mitochondrial transcription machinery in mitonuclear coevolution and speciation.
Recommended Citation
Zamudio-Ochoa, Angelica; Morozov, Yaroslav I; Sarfallah, Azadeh; Anikin, Michael; and Temiakov, Dmitry, "Mechanisms of mitochondrial promoter recognition in humans and other mammalian species" (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 212.
https://jdc.jefferson.edu/bmpfp/212
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
35191499
Language
English
Comments
This article is the author’s final published version in Nucleic Acids Research, Volume 50, Issue 5, March 2022, Pages 2765 - 2781
The published version is available at https://doi.org/10.1093/nar/gkac103. Copyright © Zamudio-Ochoa et al.