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RNA 结合蛋白:肿瘤中核基因组和线粒体基因组的协调表达。

RNA binding protein: coordinated expression between the nuclear and mitochondrial genomes in tumors.

机构信息

Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.

Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.

出版信息

J Transl Med. 2023 Jul 28;21(1):512. doi: 10.1186/s12967-023-04373-3.

Abstract

Mitochondria are the only organelles regulated by two genomes. The coordinated translation of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA), which together co-encode the subunits of the oxidative phosphorylation (OXPHOS) complex, is critical for determining the metabolic plasticity of tumor cells. RNA-binding protein (RBP) is a post-transcriptional regulatory factor that plays a pivotal role in determining the fate of mRNA. RBP rapidly and effectively reshapes the mitochondrial proteome in response to intracellular and extracellular stressors, mediating the cytoplasmic and mitochondrial translation balance to adjust mitochondrial respiratory capacity and provide energy for tumor cells to adapt to different environmental pressures and growth needs. This review highlights the ability of RBPs to use liquid-liquid phase separation (LLPS) as a platform for translation regulation, integrating nuclear-mitochondrial positive and retrograde signals to coordinate cross-department translation, reshape mitochondrial energy metabolism, and promote the development and survival of tumor cells.

摘要

线粒体是唯一受两个基因组调控的细胞器。核 DNA(nDNA)和线粒体 DNA(mtDNA)的协调翻译,共同编码氧化磷酸化(OXPHOS)复合物的亚基,对于决定肿瘤细胞的代谢可塑性至关重要。RNA 结合蛋白(RBP)是一种转录后调控因子,在决定 mRNA 的命运方面发挥着关键作用。RBP 可以快速有效地响应细胞内和细胞外应激因子重塑线粒体蛋白质组,介导细胞质和线粒体翻译平衡,调节线粒体呼吸能力,并为肿瘤细胞提供适应不同环境压力和生长需求的能量。本文综述了 RBPs 利用液-液相分离(LLPS)作为翻译调控平台的能力,整合核-线粒体正、逆行信号,协调跨部门翻译,重塑线粒体能量代谢,促进肿瘤细胞的发生和存活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b1/10386658/702043d11534/12967_2023_4373_Fig1_HTML.jpg

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