Metge Brandon J, Kammerud Sarah C, Pruitt Hawley C, Shevde Lalita A, Samant Rajeev S
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6 Avenue South, Birmingham, AL 35233, USA.
O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
iScience. 2020 Dec 30;24(1):102010. doi: 10.1016/j.isci.2020.102010. eCollection 2021 Jan 22.
Hypoxia is one of the critical stressors encountered by various cells of the human body under diverse pathophysiologic conditions including cancer and has profound impacts on several metabolic and physiologic processes. Hypoxia prompts internal ribosome entry site (IRES)-mediated translation of key genes, such as VEGF, that are vital for tumor progression. Here, we describe that hypoxia remarkably upregulates RNA Polymerase I activity. We discovered that in hypoxia, rRNA shows a different methylation pattern compared to normoxia. Heterogeneity in ribosomes due to the diversity of ribosomal RNA and protein composition has been postulated to generate "specialized ribosomes" that differentially regulate translation. We find that in hypoxia, a sub-set of differentially methylated ribosomes recognizes the VEGF-C IRES, suggesting that ribosomal heterogeneity allows for altered ribosomal functions in hypoxia.
缺氧是人体各种细胞在包括癌症在内的多种病理生理条件下所面临的关键应激源之一，对多种代谢和生理过程具有深远影响。缺氧促使内部核糖体进入位点（IRES）介导关键基因（如对肿瘤进展至关重要的VEGF）的翻译。在此，我们描述缺氧显著上调RNA聚合酶I的活性。我们发现，在缺氧条件下，与正常氧条件相比，rRNA呈现出不同的甲基化模式。由于核糖体RNA和蛋白质组成的多样性导致核糖体的异质性，据推测会产生差异调节翻译的“特殊核糖体”。我们发现，在缺氧条件下，一组差异甲基化的核糖体识别VEGF-C IRES，这表明核糖体异质性使得缺氧条件下核糖体功能发生改变。
