生物
基因表达
表达式(计算机科学)
基因
线粒体DNA
遗传学
进化生物学
计算生物学
细胞生物学
计算机科学
程序设计语言
作者
Erik McShane,Mary Couvillion,Robert Ietswaart,Gyan Prakash,Brendan M Smalec,Iliana Soto,Autum R. Baxter‐Koenigs,Karine Choquet,L. Stirling Churchman
标识
DOI:10.1016/j.molcel.2024.02.028
摘要
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.
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