Portal de Periódicos da CAPES

Base-Resolution Mapping Reveals Distinct m1A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts

2017; Elsevier BV; Volume: 68; Issue: 5 Linguagem: Inglês

10.1016/j.molcel.2017.10.019

1097-4164

Xiaoyu Li, Xushen Xiong, Meiling Zhang, Kun Wang, Ying Chen, Jun Zhou, Yuanhui Mao, Jia Lv, Danyang Yi, Xiaowei Chen, Chu Wang, Shu‐Bing Qian, Chengqi Yi,

Cancer-related molecular mechanisms research

Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.