Perspectives on topology of the human m1A methylome at single nucleotide resolution

N 1-methyladenosine was recently reported to be a chemical modification in mRNA. However, while we identified hundreds of m1A sites in the human transcriptome in a previous work, others have detected only nine sites in cytosolic and mitochondrial mRNAs. Herein, we provide additional evidence that hundreds of m1A sites are present in the human transcriptome. Moreover, we show that both the improper bioinformatic tools and the poor quality of sequencing data in a previous study led to the failure in identifying the majority of m1A sites. Our analysis hence provides an explanation of the divergence in the prevalence of this newly discovered mRNA mark.

[1]  Schraga Schwartz,et al.  m1A within cytoplasmic mRNAs at single nucleotide resolution: a reconciled transcriptome-wide map. , 2018, RNA.

[2]  Schraga Schwartz,et al.  The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution , 2017, Nature.

[3]  Todd M. Lowe,et al.  ARM-Seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments , 2015, Nature Methods.

[4]  G. Rechavi,et al.  Loud and Clear Epitranscriptomic m1A Signals: Now in Single-Base Resolution. , 2017, Molecular cell.

[5]  Mingyao Li,et al.  Widespread RNA and DNA Sequence Differences in the Human Transcriptome , 2011, Science.

[6]  R. Stroud,et al.  Crystal Structure of the Human tRNA m(1)A58 Methyltransferase-tRNA(3)(Lys) Complex: Refolding of Substrate tRNA Allows Access to the Methylation Target. , 2015, Journal of molecular biology.

[7]  T. Pan,et al.  tRNA base methylation identification and quantification via high-throughput sequencing , 2016, RNA.

[8]  Chengqi Yi,et al.  Efficient and quantitative high-throughput transfer RNA sequencing , 2015, Nature Methods.

[9]  Chengqi Yi,et al.  Base-Resolution Mapping Reveals Distinct m1A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts. , 2017, Molecular cell.

[10]  Aviv Regev,et al.  Comprehensive comparative analysis of 5’ end RNA sequencing methods , 2018, Nature Methods.

[11]  Gideon Rechavi,et al.  The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA , 2016, Nature.

[12]  Chengqi Yi,et al.  Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. , 2016, Nature chemical biology.