PDF(Pubmed)
Abstract：
Oxidative phosphorylation (OXPHOS) complexes, encoded by both mitochondrial and nuclear DNA, are essential producers of cellular ATP, but how nuclear and mitochondrial gene expression steps are coordinated to achieve balanced OXPHOS subunit biogenesis remains unresolved. Here, we present a parallel quantitative analysis of the human nuclear and mitochondrial messenger RNA (mt-mRNA) life cycles, including transcript production, processing, ribosome association, and degradation. The kinetic rates of nearly every stage of gene expression differed starkly across compartments. Compared with nuclear mRNAs, mt-mRNAs were produced 1,100-fold more, degraded 7-fold faster, and accumulated to 160-fold higher levels. Quantitative modeling and depletion of mitochondrial factors LRPPRC and FASTKD5 identified critical points of mitochondrial regulatory control, revealing that the mitonuclear expression disparities intrinsically arise from the highly polycistronic nature of human mitochondrial pre-mRNA. We propose that resolving these differences requires a 100-fold slower mitochondrial translation rate, illuminating the mitoribosome as a nexus of mitonuclear co-regulation.
摘要：
氧化磷酸化（OXPHOS）复合物，由线粒体和核DNA编码，是细胞ATP的重要生产者，但是如何协调核和线粒体基因表达步骤以实现平衡的OXPHOS亚基生物发生仍未解决。这里,我们提出了人类核和线粒体信使RNA（mt-mRNA）生命周期的平行定量分析，包括抄本制作，processing,核糖体联合，和退化。基因表达的几乎每个阶段的动力学速率在区室之间完全不同。与核mRNA相比，mt-mRNAs的产量增加了1100倍，降解速度快7倍，积累到160倍以上的水平。线粒体因子LRPPRC和FASTKD5的定量建模和消耗确定了线粒体调控的关键点，揭示了线粒体表达差异本质上是由人类线粒体pre-mRNA的高度多顺反子性质引起的。我们建议解决这些差异需要线粒体翻译速率慢100倍，将线粒体作为线粒体共调节的纽带。
