脱甲基酶
生物
癌细胞
信使核糖核酸
抄写(语言学)
核糖核酸
细胞生物学
核糖体
化学
生物化学
癌症
表观遗传学
遗传学
基因
语言学
哲学
作者
Yingmin Wu,Zhuojia Chen,Guoyou Xie,Haisheng Zhang,Zhaotong Wang,Jiawang Zhou,Feng Chen,Jiexin Li,Likun Chen,Hongxin Niu,Hongsheng Wang
标识
DOI:10.1073/pnas.2119038119
摘要
Studies on biological functions of RNA modifications such as N6-methyladenosine (m6A) in mRNA have sprung up in recent years, while the roles of N1-methyladenosine (m1A) in cancer progression remain largely unknown. We find m1A demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of adenosine 5'-triphosphate synthase, is involved in m1A demethylase ALKBH3-regulated glycolysis of cancer cells. The m1A modified A71 at the exon 1 of ATP5D negatively regulates its translation elongation via increasing the binding with YTHDF1/eRF1 complex, which facilitates the release of message RNA (mRNA) from ribosome complex. m1A also regulates mRNA stability of E2F1, which directly binds with ATP5D promoter to initiate its transcription. Targeted specific demethylation of ATP5D m1A by dm1ACRISPR system can significantly increase the expression of ATP5D and glycolysis of cancer cells. In vivo data confirm the roles of m1A/ATP5D in tumor growth and cancer progression. Our study reveals a crosstalk of mRNA m1A modification and cell metabolism, which expands the understanding of such interplays that are essential for cancer therapeutic application.
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