Title: ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing.
Authors: Zhang, Li-Sheng; Xiong, Qing-Ping; Peña Perez, Sonia; Liu, Chang; Wei, Jiangbo; Le, Cassy; Zhang, Linda; Harada, Bryan T; Dai, Qing; Feng, Xinran; Hao, Ziyang; Wang, Yuru; Dong, Xueyang; Hu, Lulu; Wang, En-Duo; Pan, Tao; Klungland, Arne; Liu, Ru-Juan; He, Chuan
Published In Nat Cell Biol, (2021 Jul)
Abstract: Members of the mammalian AlkB family are known to mediate nucleic acid demethylation1,2. ALKBH7, a mammalian AlkB homologue, localizes in mitochondria and affects metabolism3, but its function and mechanism of action are unknown. Here we report an approach to site-specifically detect N1-methyladenosine (m1A), N3-methylcytidine (m3C), N1-methylguanosine (m1G) and N2,N2-dimethylguanosine (m22G) modifications simultaneously within all cellular RNAs, and discovered that human ALKBH7 demethylates m22G and m1A within mitochondrial Ile and Leu1 pre-tRNA regions, respectively, in nascent polycistronic mitochondrial RNA4-6. We further show that ALKBH7 regulates the processing and structural dynamics of polycistronic mitochondrial RNAs. Depletion of ALKBH7 leads to increased polycistronic mitochondrial RNA processing, reduced steady-state mitochondria-encoded tRNA levels and protein translation, and notably decreased mitochondrial activity. Thus, we identify ALKBH7 as an RNA demethylase that controls nascent mitochondrial RNA processing and mitochondrial activity.
PubMed ID: 34253897
MeSH Terms: Adenosine/analogs & derivatives; Adenosine/metabolism; AlkB Enzymes/genetics; AlkB Enzymes/metabolism*; Cytidine/analogs & derivatives; Cytidine/metabolism; Guanosine/analogs & derivatives; Guanosine/metabolism; HEK293 Cells; HeLa Cells; Hep G2 Cells; Humans; Mitochondria/enzymology*; Mitochondria/genetics; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism*; Protein Biosynthesis; RNA Processing, Post-Transcriptional*; RNA, Mitochondrial/genetics; RNA, Mitochondrial/metabolism*; RNA, Transfer/genetics; RNA, Transfer/metabolism