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Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome.

Li X., Xiong X., Wang K., Wang L., Shu X., Ma S., Yi C.

N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprecipitation and the inherent ability of m(1)A to stall reverse transcription, as a means for transcriptome-wide m(1)A profiling. m(1)A-ID-seq identifies 901 m(1)A peaks (from 600 genes) in mRNA and noncoding RNA and reveals a prominent feature, enrichment in the 5' untranslated region of mRNA transcripts, that is distinct from the pattern for N(6)-methyladenosine, the most abundant internal mammalian mRNA modification. Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, we show that m(1)A methylation responds dynamically to stimuli, and we identify hundreds of stress-induced m(1)A sites. Collectively, our approaches allow comprehensive analysis of m(1)A modification and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m(1)A methylation.

Nat. Chem. Biol. 12:311-316(2016) [PubMed] [Europe PMC]

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