Open AccessALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing
Author(s) -
Lisheng Zhang,
Qing-Ping Xiong,
Sonia Peña Perez,
Chang Liu,
Jiangbo Wei,
Cassy Le,
Linda Zhang,
Bryan T. Harada,
Qing Dai,
Xinran Feng,
Ziyang Hao,
Yuru Wang,
Xu Dong,
Lulu Hu,
EnDuo Wang,
Tao Pan,
Arne Klungland,
Ru-Juan Liu,
Chuan He
Publication year - 2021
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00709-7
Subject(s) - alkb , biology , mitochondrion , transfer rna , messenger rna , rna , translation (biology) , microbiology and biotechnology , translational efficiency , demethylase , biochemistry , gene , epigenetics , dna repair
Members of the mammalian AlkB family are known to mediate nucleic acid demethylation 1,2 . ALKBH7, a mammalian AlkB homologue, localizes in mitochondria and affects metabolism 3 , but its function and mechanism of action are unknown. Here we report an approach to site-specifically detect N 1 -methyladenosine (m 1 A), N 3 -methylcytidine (m 3 C), N 1 -methylguanosine (m 1 G) and N 2 ,N 2 -dimethylguanosine (m 2 2 G) modifications simultaneously within all cellular RNAs, and discovered that human ALKBH7 demethylates m 2 2 G and m 1 A within mitochondrial Ile and Leu1 pre-tRNA regions, respectively, in nascent polycistronic mitochondrial RNA 4-6 . 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.