7pzr
Cryo-EM structure of POLRMT in free form.Cryo-EM structure of POLRMT in free form.
Structural highlights
FunctionRPOM_HUMAN DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates.[1] Publication Abstract from PubMedThe mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells. Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.,Zhu X, Xie X, Das H, Tan BG, Shi Y, Al-Behadili A, Peter B, Motori E, Valenzuela S, Posse V, Gustafsson CM, Hallberg BM, Falkenberg M Cell. 2022 Jun 23;185(13):2309-2323.e24. doi: 10.1016/j.cell.2022.05.006. Epub , 2022 Jun 2. PMID:35662414[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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