Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization

作者：Xuefeng Zhu, Xie Xie, Hrishikesh Das, Benedict G. Tan, Yonghong Shi, Ali Al-Behadili, Bradley Peter, Elisa Motori, Sebastian Valenzuela, Viktor Posse, Claes M. Gustafsson, B.M. Hallberg, Maria Falkenberg · 发表于：Cell · 年份：2022 · DOI：10.1016/j.cell.2022.05.006 · 被引用次数：68 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、Mitochondrial Function and Pathology

The 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.