报告题目：Exploring Active RNAi in Mitochondria to Reveal Epistatic Translational Control of mtDNA-Encoded Cytochrome C Oxidase Subunits
报告人：张晓荣 研究员 中国科学院生物物理研究所
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.
张晓荣，中国科学院生物物理研究所核酸生物学重点实验室研究员。主持国家自然科学基金面上项目1项，重大研究计划项目1项；科技部重点研发项目1项。以第一作者在Cell杂志发表论文1篇，以共同第一作者在Nat Struct Mol Bio杂志发表论文一篇。