Faculty and Research Interests
Dmitry Temiakov, PhD
Science Center 206B
Institute for Genetics, Russian Academy of Science, Moscow
PhD (Molecular Biology), 1996
Russian Chemical University by Mendeleev, Moscow
MS (Biotechnology), 1993
The focus of our research is to understand the molecular mechanisms of transcription and its regulation in human mitochondria. Mitochondria, the power plants of human cells, maintain their own genomes that encode proteins involved in oxidative phosphorylation. Expression of these genes is driven by a unique transcription system that involves a nuclear-encoded single subunit T7 phage-like mitochondrial RNAP polymerase (RNAP) that requires two auxiliary factors – transcription factor A (TFA) and transcription factor B2 (TFB2) for efficient initiation. Transcription in mitochondria is likely to be highly regulated, as a number of factors that affect transcription, such as MRPL12 and MTERF1-3, were recently discovered. We use an array of genetic, molecular biology, biochemical and biophysical methods to study interactions of the mitochondrial RNAP with transcription factors, and mechanisms that affect promoter recognition and fidelity. In the past, we were able to obtain crystals of other RNAPs in complex with RNA and DNA – elongation complexes of T7 RNAP and T.thermophilus RNAP. We are now working on crystallization of the human mitochondrial transcription initiation complex.
(Updated January 2017)
- Kang E, Wu J, Gutierrez NM, Koski A, Tippner-Hedges R, Agaronyan K, Platero-Luengo A, Martinez-Redondo P, Ma H, Lee Y, Hayama T, Van Dyken C, Wang X, Luo S, Ahmed R, Li Y, Ji D, Kayali R, Cinnioglu C, Olson S, Jensen J, Battaglia D, Lee D, Wu D, Huang T, Wolf DP, Temiakov D, Belmonte JC, Amato P, Mitalipov S. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature, 540 (7632): 270-5, December 2016.
- Morozov YI, Temiakov D. Human Mitochondrial Transcription Initiation Complexes Have Similar Topology on the Light and Heavy Strand Promoters. J Biol Chem, 291(26): 13432-5, June 2016.
- Morozov YI, Parshin AV, Agaronyan K, Cheung AC, Anikin M, Cramer P, Temiakov D. A model for transcription initiation in human mitochondria. Nucleic Acids Res, 43(7): 3726-35, April 2015.
- Agaronyan K, Morozov YI, Anikin M, Temiakov D. Mitochondrial biology. Replication-transcription switch in human mitochondria. Science, 347(6221): 548-51, January 2015
- Morozov YI, Agaronyan K, Cheung AC, Anikin M, Cramer P, Temiakov D. A novel intermediate in transcription initiation by human mitochondrial RNA polymerase. Nucleic Acids Res, 42(6): 3884-93, April 2014.
- Lu B, Lee J, Nie X, Li M, Morozov YI, Venkatesh S, Bogenhagen DF, Temiakov D, Suzuki CK. Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Mol Cell, 49(1):121-32, Jan 2013.
- Ochoa-Alvarez JA, Krishnan H, Shen Y, Acharya NK, Han M, McNulty DE, Hasegawa H, Hyodo T, Senga T, Geng JG, Kosciuk M, Shin SS, Goydos JS, Temiakov D, Nagele RG, Goldberg GS. Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. PLoS One, 7(7): e41845, Jul 2012.
- Ringel R, Sologub M, Morozov YI, Litonin D, Cramer P, Temiakov D. Structure of human mitochondrial RNA polymerase. Nature, 478(7368): 269-73, Sep 2011.
- 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, 285(24): 18129-33, Jun 2010.
- Sologub M, Litonin D, Anikin M, Mustaev A, Temiakov D. TFB2 is a transient component of the catalytic site of the human mitochondrial RNA polymerase. Cell, 139(5): 934-44, Nov 2009.
- Savkina M, Temiakov D, McAllister WT, Anikin M. Multiple functions of yeast mitochondrial transcription factor Mtf1p during initiation. J Biol Chem, 285(6): 3957-64, Feb 2010.
- Kent T, Kashkina E, Anikin M, Temiakov D. Maintenance of RNA-DNA hybrid length in bacterial RNA polymerases. J Biol Chem, 284(20):13497-504, May 2009.
- Sologub MIu, Kochetkov SN, Temiakov DE. [Transcription and its regulation in mammalian and human mitochondria]. Mol Biol (Mosk), 43(2): 215-29, Apr 2009.
- Kashkina E, Anikin M, Brueckner F, Lehmann E, Kochetkov SN, McAllister WT, Cramer P, Temiakov D. Multisubunit RNA polymerases melt only a single DNA base pair downstream of the active site. J Biol Chem, 282(30): 21578-82, Jul 2007.
- Kashkina E, Anikin M, Brueckner F, Pomerantz RT, McAllister WT, Cramer P, Temiakov D. Template misalignment in multisubunit RNA polymerases and transcription fidelity. Mol Cell, 24(2): 257-66, Oct 2006.
- Pomerantz RT, Temiakov D, Anikin M, Vassylyev DG, McAllister WT. A mechanism of nucleotide misincorporation during transcription due to template-strand misalignment. Mol Cell, 24(2): 245-55, Oct 2006.
- Kashkina E, Anikin M, Tahirov TH, Kochetkov SN, Vassylyev DG, Temiakov D. Elongation complexes of Thermus thermophilus RNA polymerase that possess distinct translocation conformations. Nucleic Acids Res, 34(14): 4036-45, 2006.
- Ma K, Temiakov D, Anikin M, McAllister WT. Probing conformational changes in T7 RNA polymerase during initiation and termination by using engineered disulfide linkages. Proc Natl Acad Sci USA, 102(49): 17612-7, Dec 2005.
- Temiakov D, Zenkin N, Vassylyeva MN, Perederina A, Tahirov TH, Kashkina E, Savkina M, Zorov S, Nikiforov V, Igarashi N, Matsugaki N, Wakatsuki S, Severinov K, Vassylyev DG. Structural basis of transcription inhibition by antibiotic streptolydigin. Mol Cell, 19(5): 655-66, Sep 2005.
- Temiakov D, Patlan V, Anikin M, McAllister WT, Yokoyama S, Vassylyev DG. Structural basis for substrate selection by t7 RNA polymerase. Cell,116(3): 381-91, Feb 2004.
- Temiakov D, Anikin M, Ma K, Jiang M, McAllister WT. Probing the organization of transcription complexes using photoreactive 4-thio-substituted analogs of uracil and thymidine. Methods Enzymol, 371: 133-43, 2003.
- Temiakov D, Tahirov TH, Anikin M, McAllister WT, Vassylyev DG, Yokoyama S. Crystallization and preliminary crystallographic analysis of T7 RNA polymerase elongation complex. Acta Crystallogr D Biol Crystallogr, 59(Pt 1):185-7, Jan 2003.
- Tahirov TH, Temiakov D, Anikin M, Patlan V, McAllister WT, Vassylyev DG, Yokoyama S. Structure of a T7 RNA polymerase elongation complex at 2.9 A resolution. Nature, 420(6911): 43-50, Nov 2002.
- Temiakov D, Anikin M, McAllister WT. Characterization of T7 RNA polymerase transcription complexes assembled on nucleic acid scaffolds. J Biol Chem, 277(49): 47035-43, Dec 2002.
- Ma K, Temiakov D, Jiang M, Anikin M, McAllister WT. Major conformational changes occur during the transition from an initiation complex to an elongation complex by T7 RNA polymerase. J Biol Chem, 277(45), 43206-15, Nov 2002.