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ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing

ABSTRACT: Members of the mammalian AlkB family are known to mediate nucleic acid demethylation. ALKBH7, a mammalian AlkB homologue, localizes in mitochondria (mt) and affects metabolism, but its function and mechanism of action are unknown. Here, we report an approach to site-specifically detect m1A, m3C, m1G, and m22G modifications simultaneously within all cellular RNAs, and discovered that human ALKBH7 demethylates N2, N2-dimethylguanosine (m22G) and N1-methyladenosine (m1A) within mt-Ile and mt-Leu1 pre-tRNA regions, respectively, in nascent polycistronic mt-RNA. We further show that ALKBH7 regulates the processing and structural dynamics of polycistronic mt-RNAs. Depletion of ALKBH7 leads to increased polycistronic mt-RNA processing, reduced steady-state mitochondria-encoded tRNA levels and protein translation, as well as notably decreased mitochondrial activity. Thus, we identify ALKBH7 as an RNA demethylase that controls nascent mt-RNA processing and mitochondrial activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148202 | GEO | 2021/06/02

REPOSITORIES: GEO

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