Reprogramming of m6A epitranscriptome is crucial for shaping of transcriptome and proteome in response to hypoxia. Issue 1 (2nd January 2021)

• Record Type: Journal Article
• Authors: Wang, Yan-Jie; Yang, Bing; Lai, Qiao; Shi, Jun-Fang; Peng, Jiang-Yun; Zhang, Yin; Hu, Kai-Shun; Li, Ya-Qing; Peng, Jing-Wen; Yang, Zhi-Zhi; Li, Yao-Ting; Pan, Yue; Koeffler, H. Phillip; Liao, Jian-You; Yin, Dong
• Is Part Of: RNA biology. Volume 18:Issue 1(2021)
• Page Start: 131
• Page End: 143
• Publication Date: 2021-01-02
• Subjects: Hypoxia -- m6A epitranscriptome -- trancriptome -- proteome -- ATP production; RNA -- Periodicals; Molecular biology -- Periodicals; Molecular biology; RNA; Periodicals; 572.8805
• DOI: 10.1080/15476286.2020.1804697
• Languages: English
• ISSNs: 1547-6286

Abstract

ABSTRACT: Hypoxia causes a series of responses supporting cells to survive in harsh environments. Substantial post-transcriptional and translational regulation during hypoxia has been observed. However, detailed regulatory mechanism in response to hypoxia is still far from complete. RNA m 6 A modification has been proven to govern the life cycle of RNAs. Here, we reported that total m 6 A level of mRNAs was decreased during hypoxia, which might be mediated by the induction of m 6 A eraser, ALKBH5. Meanwhile, expression levels of most YTH family members of m 6 A readers were systematically down-regulated. Transcriptome-wide analysis of m 6 A revealed a drastic reprogramming of m 6 A epitranscriptome during cellular hypoxia. Integration of m 6 A epitranscriptome with either RNA-seq based transcriptome analysis or mass spectrometry (LC-MS/MS) based proteome analysis of cells upon hypoxic stress revealed that reprogramming of m 6 A epitranscriptome reshaped the transcriptome and proteome, thereby supporting efficient generation of energy for adaption to hypoxia. Moreover, ATP production was blocked when silencing an m 6 A eraser, ALKBH5, under hypoxic condition, demonstrating that m 6 A pathway is an important regulator during hypoxic response. Collectively, our studies indicate that crosstalk between m 6 A and HIF1 pathway is essential for cellular response to hypoxia, providing insights into the underlying molecular mechanisms during hypoxia.