Transcription in human mitochondria is driven by a single-subunit, factor- dependent RNA polymerase (mtRNAP). Despite of its critical role in both expression and replication of the mitochondrial genome, transcription initiation by mtRNAP remains poorly understood. Here we report crystal structures of human mitochondrial transcription initiation complexes assembled on both light and heavy strand promoters. The structures reveal how transcription factors TFAM and TFB2M assist mtRNAP to achieve promoter-dependent initiation. TFAM tethers the N-terminal region of mtRNAP to recruit the polymerase to the promoter, whereas TFB2M induces structural changes in mtRNAP to enable promoter opening and trapping of the DNA non-template strand. Structural comparisons demonstrate that the initiation mechanism in mitochondria is distinct from that in the well-studied nuclear, bacterial, or bacteriophage transcription systems, but that similarities are found on the topological and conceptual level. These results provide a framework for studying the regulation of gene expression and DNA replication in mitochondria.
References:
1. Hillen, H.S., Morozov, Y.I., Sarfallah, A., Temiakov, D. and Cramer, P., 2017. Structural Basis of Mitochondrial Transcription Initiation. Cell, 171(5), pp.1072-1081.
2. Hillen, H.S., Parshin, A.V., Agaronyan, K., Morozov, Y.I., Graber, J.J., Chernev, A., Schwinghammer, K., Urlaub, H., Anikin, M., Cramer, P. and Temiakov, D., 2017. Mechanism of Transcription Anti-termination in Human Mitochondria. Cell, 171(5), pp.1082-1093.
Host: Alexey Amunts, amunts@localhost
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.