報告題目：Exploring Active RNAi in Mitochondria to Reveal Epistatic Translational Control of mtDNA-Encoded Cytochrome C Oxidase Subunits

報告人：張曉榮 研究員 中國科學(xué)院生物物理研究所

報告時(shí)間：2019年6月6日 上午9：00-11：00

報告地點(diǎn)：生物樓412會(huì )議室

報告內容簡(jiǎn)介：

Small interfering RNAs (siRNAs) have been widely used to post-transcriptionally silence gene expression in higher eukaryotic cells, but it is unclear whether the RNAi pathway is active within the mitochondria. The lack of such a process prevents direct perturbation of expression of mitochondrial DNA (mtDNA)-encoded genes. However, our previous studies have suggested the presence of nuclear DNA (nDNA)-encoded microRNAs (miRNAs) within mitochondria, suggesting that small RNAs can enter the mitochondrial matrix. Here we use ClickIn strategy to demonstrate entry of exogenous siRNAs into the mitochondrial matrix and their ability to specifically target individual mtDNA-encoded transcripts. Similar to miRNAs1, these siRNAs function in an Ago2 -dependent, but GW182-independent manner; however, unlike the function of miRNA, the siRNA effect requires the slicing activity of Ago2 within mitochondria. Using Mito-RNAi, we investigated the direct contribution of mtDNA-encoded gene products to the coordinated assembly of respiratory chain complexes, unexpectedly revealing sequential translational control of cytochrome c oxidase subunit I (COXI) by COXII, and both COXI and COXII by COXIII. These findings demonstrate an active RNAi system within the mitochondrial matrix and extend the concept of mitochondrial translational plasticity previously established with imported nDNA encoded subunits to mtDNA-encoded components to achieve epistatic regulation of a respiratory complex.

報告人簡(jiǎn)介：

張曉榮，中國科學(xué)院生物物理研究所核酸生物學(xué)重點(diǎn)實(shí)驗室研究員。主持國家自然科學(xué)基金面上項目1項，重大研究計劃項目1項；科技部重點(diǎn)研發(fā)項目1項。以第一作者在Cell雜志發(fā)表論文1篇，以共同第一作者在Nat Struct Mol Bio雜志發(fā)表論文一篇。