Abstract
Oxygen shortage, known as hypoxia, occurs commonly in both physiological and pathological conditions. Transcriptional regulation by hypoxia-inducible factors (HIFs) is a dominant regulatory mechanism controlling hypoxia-responsive genes during acute hypoxia; however, recent studies suggest that post-transcriptional regulation, including RNA degradation, also involves hypoxia-induced gene expression during the chronic hypoxia. In this study, we developed a method to quantify the contributions of RNA synthesis and degradation to differential gene expression, and identified 102 genes mainly regulated via RNA degradation under chronic hypoxia in HCT116 cells. Bioinformatics analysis showed that the genes mainly regulated by RNA degradation were involved in glycolysis. Combinatory analysis of experimental approach using RNA interactome capture and statistical analysis using public databases, and followed depletion assays identified that an RNA-binding protein fragile X mental retardation protein (FMRP) enhances the expression of mRNAs encoding rate-limiting enzymes for glycolysis under chronic hypoxia. This study emphasizes the importance of post-transcriptional gene regulation under chronic hypoxia.