2. Academic Validation
  3. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome

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

  • Nat Chem Biol. 2016 May;12(5):311-6. doi: 10.1038/nchembio.2040.
Xiaoyu Li 1 2,  Xushen Xiong 1 2 3,  Kun Wang 1 2,  Lixia Wang 1 2,  Xiaoting Shu 1 2 3,  Shiqing Ma 1 2 3,  Chengqi Yi 1 2 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
  • 2 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 3 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 4 Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
PMID: 26863410 DOI: 10.1038/nchembio.2040
Abstract

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.

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