Reprogramming of m6A epitranscriptome is crucial for shaping of transcriptome and proteome in response to hypoxia
| Autor: | 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 |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Epigenomics Adenosine Proteome Physiological proteome 1.1 Normal biological development and functioning Stress Cell Line trancriptome Genetic Tandem Mass Spectrometry Underpinning research Genetics Humans 2.1 Biological and endogenous factors Aetiology Hypoxia Chromatography Liquid Tumor Gene Expression Profiling Human Genome Computational Biology m6A epitranscriptome m(6)A epitranscriptome Gene Ontology ATP production Gene Expression Regulation Gene Knockdown Techniques Generic health relevance Transcriptome Epigenesis Developmental Biology |
| Zdroj: | RNA biology, vol 18, iss 1 |
| Popis: | 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 m6A modification has been proven to govern the life cycle of RNAs. Here, we reported that total m6A level of mRNAs was decreased during hypoxia, which might be mediated by the induction of m6A eraser, ALKBH5. Meanwhile, expression levels of most YTH family members of m6A readers were systematically down-regulated. Transcriptome-wide analysis of m6A revealed a drastic reprogramming of m6A epitranscriptome during cellular hypoxia. Integration of m6A 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 m6A epitranscriptome reshaped the transcriptome and proteome, thereby supporting efficient generation of energy for adaption to hypoxia. Moreover, ATP production was blocked when silencing an m6A eraser, ALKBH5, under hypoxic condition, demonstrating that m6A pathway is an important regulator during hypoxic response. Collectively, our studies indicate that crosstalk between m6A and HIF1 pathway is essential for cellular response to hypoxia, providing insights into the underlying molecular mechanisms during hypoxia. |
| Databáze: | OpenAIRE |
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