Structural highlights
Function
[TFB2M_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity. Compared to TFB1M, it activates transcription of mitochondrial DNA more efficiently, while it has less methyltransferase activity.[1] [2] [3] [4]
Publication Abstract from PubMed
Transcription in human mitochondria is driven by a single-subunit, factor-dependent RNA polymerase (mtRNAP). Despite 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.
Structural Basis of Mitochondrial Transcription Initiation.,Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P Cell. 2017 Nov 16;171(5):1072-1081.e10. doi: 10.1016/j.cell.2017.10.036. PMID:29149603[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM. Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet. 2002 Jul;31(3):289-94. Epub 2002 Jun 17. PMID:12068295 doi:http://dx.doi.org/10.1038/ng909
- ↑ McCulloch V, Shadel GS. Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity. Mol Cell Biol. 2003 Aug;23(16):5816-24. PMID:12897151
- ↑ Gaspari M, Falkenberg M, Larsson NG, Gustafsson CM. The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells. EMBO J. 2004 Nov 24;23(23):4606-14. Epub 2004 Nov 4. PMID:15526033 doi:http://dx.doi.org/7600465
- ↑ Litonin D, Sologub M, Shi Y, Savkina M, Anikin M, Falkenberg M, Gustafsson CM, Temiakov D. Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem. 2010 Jun 11;285(24):18129-33. doi: 10.1074/jbc.C110.128918. Epub, 2010 Apr 21. PMID:20410300 doi:http://dx.doi.org/10.1074/jbc.C110.128918
- ↑ Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P. Structural Basis of Mitochondrial Transcription Initiation. Cell. 2017 Nov 16;171(5):1072-1081.e10. doi: 10.1016/j.cell.2017.10.036. PMID:29149603 doi:http://dx.doi.org/10.1016/j.cell.2017.10.036
