Base-Resolution Mapping Reveals Distinct m 1 A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts.

Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1 -methyladenosine (m1 A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m1 A profiling method, based on m1 A-induced misincorporation during reverse transcription, and report distinct classes of m1 A methylome in the human transcriptome. m1 A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m1 A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m1 A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1 A level via TRMT61B, a mitochondria-localizing m1 A methyltransferase, demonstrates that m1 A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1 A methylome and provide a resource for functional studies of m1 A-mediated epitranscriptomic regulation.