| Literature DB >> 34253897 |
Li-Sheng Zhang1,2, Qing-Ping Xiong3, Sonia Peña Perez4,5, Chang Liu1,2, Jiangbo Wei1,2, Cassy Le4, Linda Zhang1,2, Bryan T Harada1,2, Qing Dai1,2, Xinran Feng1,2, Ziyang Hao1,2, Yuru Wang6, Xueyang Dong1,2, Lulu Hu1,2, En-Duo Wang3,7, Tao Pan6, Arne Klungland4,5, Ru-Juan Liu8,9, Chuan He10,11,12.
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.Entities:
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Year: 2021 PMID： 34253897 PMCID： PMC8716185 DOI： 10.1038/s41556-021-00709-7
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.213