| Structural highlights
Function
[TEFM_HUMAN] Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery.[1] [RPOM_HUMAN] DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates.[2]
Publication Abstract from PubMed
In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp," providing high processivity to the EC. TEFM also binds near the RNA exit channel to prevent formation of the RNA G-quadruplex structure required for termination and thus synthesis of the replication primer. Our data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mtDNA.
Mechanism of Transcription Anti-termination in Human Mitochondria.,Hillen HS, Parshin AV, Agaronyan K, Morozov YI, Graber JJ, Chernev A, Schwinghammer K, Urlaub H, Anikin M, Cramer P, Temiakov D Cell. 2017 Oct 7. pii: S0092-8674(17)31129-7. doi: 10.1016/j.cell.2017.09.035. PMID:29033127[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Minczuk M, He J, Duch AM, Ettema TJ, Chlebowski A, Dzionek K, Nijtmans LG, Huynen MA, Holt IJ. TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res. 2011 May;39(10):4284-99. doi: 10.1093/nar/gkq1224. Epub 2011, Jan 28. PMID:21278163 doi:10.1093/nar/gkq1224
- ↑ Minczuk M, He J, Duch AM, Ettema TJ, Chlebowski A, Dzionek K, Nijtmans LG, Huynen MA, Holt IJ. TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res. 2011 May;39(10):4284-99. doi: 10.1093/nar/gkq1224. Epub 2011, Jan 28. PMID:21278163 doi:10.1093/nar/gkq1224
- ↑ Hillen HS, Parshin AV, Agaronyan K, Morozov YI, Graber JJ, Chernev A, Schwinghammer K, Urlaub H, Anikin M, Cramer P, Temiakov D. Mechanism of Transcription Anti-termination in Human Mitochondria. Cell. 2017 Oct 7. pii: S0092-8674(17)31129-7. doi: 10.1016/j.cell.2017.09.035. PMID:29033127 doi:http://dx.doi.org/10.1016/j.cell.2017.09.035
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